{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:29:11Z","timestamp":1788298151462,"version":"build-2803163510"},"reference-count":141,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015690","name":"Unpad","doi-asserted-by":"publisher","award":["No. 4303\/ B3\/DT.03.08\/2025 and 3927\/UN6. RKT\/HK.07.00\/2025"],"award-info":[{"award-number":["No. 4303\/ B3\/DT.03.08\/2025 and 3927\/UN6. RKT\/HK.07.00\/2025"]}],"id":[{"id":"10.13039\/501100015690","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BUPP Unpad","award":["no. 5089\/UN6.3.1\/PT.00\/2024"],"award-info":[{"award-number":["no. 5089\/UN6.3.1\/PT.00\/2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Prostate cancer remains a leading cause of male cancer-related mortality, largely driven by the dysregulated activation of the androgen receptor (AR) signaling pathway. The emergence of resistance, particularly in castration-resistant prostate cancer (CRPC), necessitates the discovery of innovative therapeutic approaches. This systematic review aims to consolidate contemporary evidence regarding natural products as bioactive alternatives capable of targeting the AR signaling axis. Methods: Adhering to PRISMA guidelines, a systematic search was conducted across PubMed, Scopus, and ScienceDirect databases. The review identified and qualitatively analyzed 15 original research studies that investigated the efficacy and mechanisms of various natural compounds in modulating AR signaling. Results: The analysis reveals that natural products deactivate the AR signaling axis through diverse mechanisms. Neoisoliquiritin and \u03b1-terthienyl were found to suppress AR expression, activity, and nuclear translocation. Notably, \u03b1-mangostin facilitates the degradation of the AR-V7 splice variant, a key driver of treatment resistance. Manzamine A inhibits AR biosynthesis by targeting the transcription factor E2F8. Furthermore, alternative pathways are modulated through 5-\u03b1-reductase inhibition (Annona muricata compounds) and the activation of the non-classical membrane receptor ZIP9 by (-)-epicatechin to induce apoptosis. Conclusions: The emergence of resistance, particularly in castration-resistant prostate cancer (CRPC), necessitates the exploration of innovative therapeutic approaches. This systematic review consolidates contemporary evidence regarding natural products as potential bioactive alternatives for modulating the androgen receptor (AR) signaling axis. Rather than providing a definitive clinical roadmap, this work establishes a preclinical framework for identifying substances that may deactivate the receptor, break down its resistant forms, or prevent nuclear translocation.<\/jats:p>","DOI":"10.3390\/cancers18050786","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T16:18:45Z","timestamp":1772554725000},"page":"786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bioactive Natural Products Targeting Androgen Receptor Signaling in Prostate Cancer: A Systematic Review"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2551-919X","authenticated-orcid":false,"given":"Febby","family":"Pratama","sequence":"first","affiliation":[{"name":"Departement of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jl Ir. Soekarno KM 21, Jatinangor 45363, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhania","family":"Novitasari","sequence":"additional","affiliation":[{"name":"Departement of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jl Ir. Soekarno KM 21, Jatinangor 45363, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa","family":"Mardianingrum","sequence":"additional","affiliation":[{"name":"Departement of Pharmacy, Faculty of Health Sciences, Universitas Perjuangan, Jl Peta 177, Tasikmalaya 46115, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1303-8812","authenticated-orcid":false,"given":"Holis Abdul","family":"Holik","sequence":"additional","affiliation":[{"name":"Departement of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jl Ir. Soekarno KM 21, Jatinangor 45363, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4953-927X","authenticated-orcid":false,"given":"Nur Kusaira Khairul","family":"Ikram","sequence":"additional","affiliation":[{"name":"Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6156-8025","authenticated-orcid":false,"given":"Muchtaridi","family":"Muchtaridi","sequence":"additional","affiliation":[{"name":"Departement of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jl Ir. Soekarno KM 21, Jatinangor 45363, Indonesia"},{"name":"Research Collaboration Centre for Radiopharmaceuticals Theranostic, National Research and Innovation Agency (BRIN), Sumedang 45363, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","first-page":"64","article-title":"Global burden of benign prostatic hyperplasia, urinary tract infections, urolithiasis, bladder cancer, kidney cancer, and prostate cancer from 1990 to 2021","volume":"11","author":"Zi","year":"2024","journal-title":"Mil. Med. Res."},{"key":"ref_2","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ismuha, R.R., Ritawidya, R., Daruwati, I., and Muchtaridi, M. (2024). Future Prospect of Low-Molecular-Weight Prostate-Specific Membrane Antigen Radioisotopes Labeled as Theranostic Agents for Metastatic Castration-Resistant Prostate Cancer. Molecules, 29.","DOI":"10.3390\/molecules29246062"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/s41388-020-01598-0","article-title":"Loss and revival of androgen receptor signaling in advanced prostate cancer","volume":"40","author":"Formaggio","year":"2021","journal-title":"Oncogene"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"109501","DOI":"10.1016\/j.steroids.2024.109501","article-title":"Structural perspectives on the androgen receptor, the elusive shape-shifter","volume":"211","author":"Johnson","year":"2024","journal-title":"Steroids"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Banerjee, P.P., and Srivastava, S. (2024). Androgen Receptor Signaling: A Central and Evolving Theme in Prostate Cancer Treatment. Handbook of Oncobiology: From Basic to Clinical Sciences, Springer.","DOI":"10.1007\/978-981-99-6263-1_24"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"R143","DOI":"10.1530\/ERC-22-0140","article-title":"Androgen receptor mutations for precision medicine in prostate cancer","volume":"29","author":"Shiota","year":"2022","journal-title":"Endocr.-Relat. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/s41591-022-01717-2","article-title":"Delivering precision oncology to patients with cancer","volume":"28","author":"Mateo","year":"2022","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Mohler, M.L., Sikdar, A., Ponnusamy, S., Hwang, D.-J., He, Y., Miller, D.D., and Narayanan, R. (2021). An Overview of Next-Generation Androgen Receptor-Targeted Therapeutics in Development for the Treatment of Prostate Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22042124"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s13205-023-03636-6","article-title":"Vinca alkaloids as a potential cancer therapeutics: Recent update and future challenges","volume":"13","author":"Banyal","year":"2023","journal-title":"3 Biotech"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1080\/13543776.2023.2265561","article-title":"Natural products as a source of new anticancer chemotypes","volume":"33","author":"Melfi","year":"2023","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sun, R., Guo, F., Zhang, Y., Shao, H., Yang, X., Wang, C., and Yang, C. (2025). Biological activity of secondary metabolites of actinomycetes and their potential sources as antineoplastic drugs: A review. Front. Microbiol., 16.","DOI":"10.3389\/fmicb.2025.1550516"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ni\u017enansk\u00fd, \u013d., Osinov\u00e1, D., Kuruc, R., Hengerics Szab\u00f3, A., Sz\u00f3r\u00e1dov\u00e1, A., Mas\u00e1r, M., and Ni\u017enansk\u00e1, \u017d. (2022). Natural Taxanes: From Plant Composition to Human Pharmacology and Toxicity. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415619"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100040","DOI":"10.1016\/j.oor.2023.100040","article-title":"Cancer treatment: Role of natural products. Time to have a serious rethink","volume":"6","author":"Mali","year":"2023","journal-title":"Oral Oncol. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s13237-022-00405-3","article-title":"Plant-derived natural products for drug discovery: Current approaches and prospects","volume":"65","author":"Nasim","year":"2022","journal-title":"Nucleus"},{"key":"ref_16","first-page":"641","article-title":"The role of alternative medicine and complimentary therapies in urologic disease: New horizons","volume":"91","author":"Bizzarri","year":"2024","journal-title":"Urol. J."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kristoffersen, A.E., Nilsen, J.V., Stub, T., Nordberg, J.H., Wider, B., Mora, D., Nakandi, K., and Bjelland, M. (2022). Use of Complementary and Alternative Medicine in the context of cancer; prevalence, reasons for use, disclosure, information received, risks and benefits reported by people with cancer in Norway. BMC Complement. Med. Ther., 22.","DOI":"10.1186\/s12906-022-03606-0"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Majrashi, T.A., Alshehri, S.A., Alsayari, A., Muhsinah, A.B., Alrouji, M., Alshahrani, A.M., Shamsi, A., and Atiya, A. (2023). Insight into the Biological Roles and Mechanisms of Phytochemicals in Different Types of Cancer: Targeting Cancer Therapeutics. Nutrients, 15.","DOI":"10.3390\/nu15071704"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Das Talukdar, A., Patra, J.K., Das, G., and Nath, D. (2024). Economic Benefits of Natural Products in Modern Drug Discovery in the Twenty-First Century. Traditional Resources and Tools for Modern Drug Discovery: Ethnomedicine and Pharmacology, Springer Nature.","DOI":"10.1007\/978-981-97-4600-2"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"440","DOI":"10.22159\/ajpcr.2017.v10i12.20812","article-title":"Anticancer potential of \u03b1-mangostin","volume":"10","author":"Muchtaridi","year":"2017","journal-title":"Asian J. Pharm. Clin. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Herdiana, Y., Wathoni, N., Shamsuddin, S., and Muchtaridi, M. (2021). \u03b1-Mangostin Nanoparticles Cytotoxicity and Cell Death Modalities in Breast Cancer Cell Lines. Molecules, 26.","DOI":"10.3390\/molecules26175119"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Dewi, C., Fristiohady, A., Amalia, R., Ikram, N.K.K., Ibrahim, S., and Muchtaridi, M. (2022). Signaling Pathways and Natural Compounds in Triple-Negative Breast Cancer Cell Line. Molecules, 27.","DOI":"10.3390\/molecules27123661"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s12943-024-02119-3","article-title":"Altered metabolism in cancer: Insights into energy pathways and therapeutic targets","volume":"23","author":"Tufail","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1080\/10942912.2016.1220393","article-title":"Natural polyphenols: An overview","volume":"20","author":"Abbas","year":"2017","journal-title":"Int. J. Food Prop."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7619","DOI":"10.21037\/tcr-20-2359","article-title":"Functions of polyphenols and its anticancer properties in biomedical research: A narrative review","volume":"9","author":"Bhosale","year":"2020","journal-title":"Transl. Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"153514","DOI":"10.1016\/j.phymed.2021.153514","article-title":"Neoisoliquiritin exerts tumor suppressive effects on prostate cancer by repressing androgen receptor activity","volume":"85","author":"Chen","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Basavaraj, P., Ruangsai, P., Hsieh, P.-F., Jiang, W.-P., Bau, D.-T., Huang, G.-J., and Huang, W.-C. (2022). Alpinumisoflavone Exhibits the Therapeutic Effect on Prostate Cancer Cells by Repressing AR and Co-Targeting FASN- and HMGCR-Mediated Lipid and Cholesterol Biosynthesis. Life, 12.","DOI":"10.3390\/life12111769"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Huang, S.-Y., Chang, S.-F., Chau, S.-F., and Chiu, S.-C. (2019). The Protective Effect of Hispidin against Hydrogen Peroxide-Induced Oxidative Stress in ARPE-19 Cells via Nrf2 Signaling Pathway. Biomolecules, 9.","DOI":"10.3390\/biom9080380"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s12272-023-01461-2","article-title":"Androgen receptor and hyaluronan-mediated motility receptor as new molecular targets of baicalein: New molecular mechanisms for its anticancer properties","volume":"46","author":"Jiang","year":"2023","journal-title":"Arch. Pharmacal Res."},{"key":"ref_30","first-page":"6422500","article-title":"Citrus Flavone Tangeretin Inhibits CRPC Cell Proliferation by Regulating Cx26, AKT, and AR Signaling","volume":"2022","author":"Zhang","year":"2022","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"105906","DOI":"10.1016\/j.jsbmb.2021.105906","article-title":"(-)-Epicatechin acts as a potent agonist of the membrane androgen receptor, ZIP9 (SLC39A9), to promote apoptosis of breast and prostate cancer cells","volume":"211","author":"Thomas","year":"2021","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Majeed Malik, I., Hussain Bhat, A., Majeed, D., and Nabi, N. (2025). Environmental Factors Influencing Phytochemical Production for Enhanced Phytochemical Defense. Phytochemical Arsenal: Understanding Plant Defense Mechanisms Against Nematodes, Bentham Science Publishers.","DOI":"10.2174\/9789815322675125010009"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Rudzi\u0144ska, A., Juchaniuk, P., Oberda, J., Wi\u015bniewska, J., Wojdan, W., Szklener, K., and Ma\u0144dziuk, S. (2023). Phytochemicals in Cancer Treatment and Cancer Prevention\u2014Review on Epidemiological Data and Clinical Trials. Nutrients, 15.","DOI":"10.3390\/nu15081896"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ahmed, M.B., Islam, S.U., Alghamdi, A.A.A., Kamran, M., Ahsan, H., and Lee, Y.S. (2022). Phytochemicals as Chemo-Preventive Agents and Signaling Molecule Modulators: Current Role in Cancer Therapeutics and Inflammation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415765"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Jang, J.-H., and Lee, T.-J. (2023). Mechanisms of Phytochemicals in Anti-Inflammatory and Anti-Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24097863"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Oyenihi, O.R., Oyenihi, A.B., Erhabor, J.O., Matsabisa, M.G., and Oguntibeju, O.O. (2021). Unravelling the Anticancer Mechanisms of Traditional Herbal Medicines with Metabolomics. Molecules, 26.","DOI":"10.3390\/molecules26216541"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/s41568-022-00544-4","article-title":"Mechanisms driving the immunoregulatory function of cancer cells","volume":"23","year":"2023","journal-title":"Nat. Rev. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"122","DOI":"10.2174\/138945011793591626","article-title":"Complex Interactions between Phytochemicals. The Multi-Target Therapeutic Concept of Phytotherapy","volume":"12","author":"Efferth","year":"2011","journal-title":"Curr. Drug Targets"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"20931","DOI":"10.1038\/s41598-025-05659-w","article-title":"ZFHX3 is integral to androgen\/AR signaling involving protein association with AR in prostate cancer cells","volume":"15","author":"Fu","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/s41392-022-01042-7","article-title":"Targeting signaling pathways in prostate cancer: Mechanisms and clinical trials","volume":"7","author":"He","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Jacob, A., Raj, R., Allison, D.B., and Myint, Z.W. (2021). Androgen Receptor Signaling in Prostate Cancer and Therapeutic Strategies. Cancers, 13.","DOI":"10.20944\/preprints202110.0016.v1"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Labaf, M., Li, M., Ting, L., Karno, B., Zhang, S., Gao, S., Patalano, S., Macoska, J.A., Zarringhalam, K., and Han, D. (2022). Increased AR expression in castration-resistant prostate cancer rapidly induces AR signaling reprogramming with the collaboration of EZH2. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1021845"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1038\/s41598-021-81164-0","article-title":"Androgen receptor and its splice variant, AR-V7, differentially induce mRNA splicing in prostate cancer cells","volume":"11","author":"Rana","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_44","first-page":"398","article-title":"Androgen deprivation therapy in localized prostate cancer. Current status and future trends","volume":"47","author":"Fernandez","year":"2023","journal-title":"Actas Ur\u00f3l. Esp. (Engl. Ed.)"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Harris, A.E., Metzler, V.M., Lothion-Roy, J., Varun, D., Woodcock, C.L., Haigh, D.B., Endeley, C., Haque, M., Toss, M.S., and Alsaleem, M. (2022). Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1006101"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Facchini, G., D\u2019Arienzo, A., Nicastro, A., Flauto, F., Izzo, M., Montella, L., Riccardo, F., Fusco, G.M., Trama, F., and Lauro, G.D. (2025). Apalutamide Monotherapy in Metastatic Hormone-Sensitive Prostate Cancer: A Viable Alternative to First-Generation Anti-Androgen Agents to Avoid the Flare Phenomenon and an Effective Treatment for Achieving Early PSA Response. Cancers, 17.","DOI":"10.3390\/cancers17152573"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kocic, G., Hadzi-Djokic, J., and Simic, T. (2024). Hormone Therapy for Advanced Prostate Cancer. Prostate Cancer: Advancements in the Pathogenesis, Diagnosis and Personalized Therapy, Springer Nature.","DOI":"10.1007\/978-3-031-51712-9"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1080\/14656566.2022.2033210","article-title":"Advances with androgen deprivation therapy for prostate cancer","volume":"23","author":"Yu","year":"2022","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Huang, J., Lin, B., and Li, B. (2022). Anti-Androgen Receptor Therapies in Prostate Cancer: A Brief Update and Perspective. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.865350"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kuzminac, I.Z., Nikoli\u0107, A.R., Savi\u0107, M.P., and Ajdukovi\u0107, J.J. (2024). Abiraterone and Galeterone, Powerful Tools Against Prostate Cancer: Present and Perspective. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16111401"},{"key":"ref_51","unstructured":"Sharma, K. (2024). Identification and Targeting of Novel Mechanisms for Treatment of Castration Resistant Prostate Cancer (CRPC). [Ph.D. Thesis, Universit\u00e4t Bern]."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"106446","DOI":"10.1016\/j.jsbmb.2023.106446","article-title":"Prostate cancer androgen biosynthesis relies solely on CYP17A1 downstream metabolites","volume":"236","author":"Snaterse","year":"2024","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Wang, B.-R., Chen, Y.-A., Kao, W.-H., Lai, C.-H., Lin, H., and Hsieh, J.-T. (2022). Developing New Treatment Options for Castration-Resistant Prostate Cancer and Recurrent Disease. Biomedicines, 10.","DOI":"10.3390\/biomedicines10081872"},{"key":"ref_54","first-page":"457","article-title":"A Review of the Pathophysiological Mechanisms Underlying Castration-resistant Prostate Cancer","volume":"13","author":"Crowley","year":"2021","journal-title":"Res. Rep. Urol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Pozas, J., \u00c1lvarez Rodr\u00edguez, S., Fern\u00e1ndez, V.A., Burgos, J., Santoni, M., Manneh Kopp, R., Molina-Cerrillo, J., and Alonso-Gordoa, T. (2022). Androgen Receptor Signaling Inhibition in Advanced Castration Resistance Prostate Cancer: What Is Expected for the Near Future?. Cancers, 14.","DOI":"10.3390\/cancers14246071"},{"key":"ref_56","first-page":"211","article-title":"Androgen Receptor Signalling in Prostate Cancer: Mechanisms of Resistance to Endocrine Therapies","volume":"17","author":"Quistini","year":"2025","journal-title":"Res. Rep. Urol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e454","DOI":"10.1136\/bmjspcare-2021-003098","article-title":"Androgen deprivation therapy and radiation for prostate cancer\u2014Cognitive impairment, sleep, symptom burden: A prospective study","volume":"13","author":"Tulk","year":"2023","journal-title":"BMJ Support. Palliat. Care"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/s41391-021-00450-0","article-title":"Supervised exercise therapy compared with no exercise therapy to reverse debilitating effects of androgen deprivation therapy in patients with prostate cancer: A systematic review and meta-analysis","volume":"25","author":"Ussing","year":"2022","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Naithani, U., and Guleria, V. (2024). Integrative computational approaches for discovery and evaluation of lead compound for drug design. Front. Drug Discov., 4.","DOI":"10.3389\/fddsv.2024.1362456"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1007\/s11030-021-10217-3","article-title":"Artificial intelligence to deep learning: Machine intelligence approach for drug discovery","volume":"25","author":"Gupta","year":"2021","journal-title":"Mol. Divers."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1007\/s13346-023-01327-6","article-title":"Role of three-dimensional cell culture in therapeutics and diagnostics: An updated review","volume":"13","author":"Biju","year":"2023","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Niazi, S.K. (2023). A Critical Analysis of the FDA\u2019s Omics-Driven Pharmacodynamic Biomarkers to Establish Biosimilarity. Pharmaceuticals, 16.","DOI":"10.3390\/ph16111556"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Kim, C., and Kim, B. (2018). Anti-Cancer Natural Products and Their Bioactive Compounds Inducing ER Stress-Mediated Apoptosis: A Review. Nutrients, 10.","DOI":"10.3390\/nu10081021"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.semcancer.2016.06.003","article-title":"Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer","volume":"40\u201341","author":"Kallifatidis","year":"2016","journal-title":"Semin. Cancer Biol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Makino, T., Izumi, K., and Mizokami, A. (2021). Undesirable Status of Prostate Cancer Cells after Intensive Inhibition of AR Signaling: Post-AR Era of CRPC Treatment. Biomedicines, 9.","DOI":"10.3390\/biomedicines9040414"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Zhang, Y.-L., Chen, G.-L., Liu, Y., Zhuang, X.-C., and Guo, M.-Q. (2021). Stimulation of ROS Generation by Extract of Warburgia ugandensis Leading to G0\/G1 Cell Cycle Arrest and Antiproliferation in A549 Cells. Antioxidants, 10.","DOI":"10.3390\/antiox10101559"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Siciliano, T., Simons, I.H., Beier, A.-M.K., Ebersbach, C., Aksoy, C., Seed, R.I., Stope, M.B., Thomas, C., and Erb, H.H.H. (2021). A Systematic Comparison of Antiandrogens Identifies Androgen Receptor Protein Stability as an Indicator for Treatment Response. Life, 11.","DOI":"10.3390\/life11090874"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.eururo.2018.02.019","article-title":"Patient-derived Hormone-naive Prostate Cancer Xenograft Models Reveal Growth Factor Receptor Bound Protein 10 as an Androgen Receptor-repressed Gene Driving the Development of Castration-resistant Prostate Cancer","volume":"73","author":"Hao","year":"2018","journal-title":"Eur. Urol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Devlies, W., Handle, F., Devos, G., Joniau, S., and Claessens, F. (2021). Preclinical Models in Prostate Cancer: Resistance to AR Targeting Therapies in Prostate Cancer. Cancers, 13.","DOI":"10.3390\/cancers13040915"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Beretta, G.L., and Zaffaroni, N. (2019). Androgen Receptor-Directed Molecular Conjugates for Targeting Prostate Cancer. Front. Chem., 7.","DOI":"10.3389\/fchem.2019.00369"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Lee, S., Hoang, G.D., Kim, D., Song, H.S., Choi, S., Lee, D., and Kang, K.S. (2021). Efficacy of Alpinumisoflavone Isolated from Maclura tricuspidata Fruit in Tumor Necrosis Factor-\u03b1-Induced Damage of Human Dermal Fibroblasts. Antioxidants, 10.","DOI":"10.3390\/antiox10040514"},{"key":"ref_72","first-page":"999","article-title":"Alpinumisoflavone suppresses tumour growth and metastasis of clear-cell renal cell carcinoma","volume":"7","author":"Wang","year":"2017","journal-title":"Am. J. Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Ateba, S.B., Mvondo, M.A., Djiogue, S., Zingu\u00e9, S., Krenn, L., and Njamen, D. (2019). A Pharmacological Overview of Alpinumisoflavone, a Natural Prenylated Isoflavonoid. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00952"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Chan, K.C., Basavaraj, P., Tsai, J.C., Viehoever, J., Hsieh, B.Y., Li, X.Y., Huang, G.J., and Huang, W.C. (2024). Evaluating the Therapeutic Effect of Hispidin on Prostate Cancer Cells. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25147857"},{"key":"ref_75","first-page":"262195","article-title":"Matrix metalloproteinases 2 and 9 immunoexpression in prostate carcinoma at the positive margin of radical prostatectomy specimens","volume":"2014","year":"2014","journal-title":"Pathol. Res. Int."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1111\/j.1365-2605.2009.01016.x","article-title":"Matrix metalloproteinase (MMP)-2 and MMP-9 activity and localization during ventral prostate atrophy and regrowth","volume":"33","author":"Justulin","year":"2010","journal-title":"Int. J. Androl."},{"key":"ref_77","first-page":"5865","article-title":"The relationship between MMP-2 and MMP-9 expression levels with breast cancer incidence and prognosis","volume":"14","author":"Li","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Shoari, A., Ashja Ardalan, A., Dimesa, A.M., and Coban, M.A. (2024). Targeting Invasion: The Role of MMP-2 and MMP-9 Inhibition in Colorectal Cancer Therapy. Biomolecules, 15.","DOI":"10.3390\/biom15010035"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"M\u0142ynarczyk, G., Gudowska-Sawczuk, M., Mroczko, B., Bruczko-Goralewska, M., Romanowicz, L., and Tokarzewicz, A. (2023). Higher Content but No Specific Activity in Gelatinase B (MMP-9) Compared with Gelatinase A (MMP-2) in Human Renal Carcinoma. Cancers, 15.","DOI":"10.3390\/cancers15225475"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"107347","DOI":"10.1016\/j.jbc.2024.107347","article-title":"Extracellular proteolysis in cancer: Proteases, substrates, and mechanisms in tumor progression and metastasis","volume":"300","author":"Radisky","year":"2024","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"350","DOI":"10.4111\/icu.20210411","article-title":"Atorvastatin regulates the migration and invasion of prostate cancer through the epithelial-mesenchymal transformation and matrix metalloproteinase pathways","volume":"63","author":"Zhu","year":"2022","journal-title":"Investig. Clin. Urol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Tiwari, A., Mukherjee, B., Hassan, M.K., Pattanaik, N., Jaiswal, A.M., and Dixit, M. (2019). Reduced FRG1 expression promotes prostate cancer progression and affects prostate cancer cell migration and invasion. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-5509-4"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13045-023-01512-7","article-title":"Reactive oxygen species (ROS) scavenging biomaterials for anti-inflammatory diseases: From mechanism to therapy","volume":"16","author":"Liu","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Chen, J., Gou, Z., Yang, G., Zhou, L., Kim, A.N., Shi, W., and Zhou, Y. (2025). Ferroptosis, a Distinct Form of Cell Death, and Research Progress on Its Modulators. Pharmaceuticals, 18.","DOI":"10.3390\/ph18121785"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.1093\/nar\/gkq1352","article-title":"USP10 deubiquitylates the histone variant H2A.Z and both are required for androgen receptor-mediated gene activation","volume":"39","author":"Draker","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Liu, H., Dong, Y., Gao, Y., Du, Z., Wang, Y., Cheng, P., Chen, A., and Huang, H. (2016). The Fascinating Effects of Baicalein on Cancer: A Review. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17101681"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Morshed, A.K.M.H., Paul, S., Hossain, A., Basak, T., Hossain, M.S., Hasan, M.M., Hasibuzzaman, M.A., Rahaman, T.I., Mia, M.A.R., and Shing, P. (2023). Baicalein as Promising Anticancer Agent: A Comprehensive Analysis on Molecular Mechanisms and Therapeutic Perspectives. Cancers, 15.","DOI":"10.3390\/cancers15072128"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"101712","DOI":"10.1016\/j.tranon.2023.101712","article-title":"Connexin43 is associated with the progression of clear cell renal carcinoma and is regulated by tangeretin to sygergize with tyrosine kinase inhibitors","volume":"35","author":"Lai","year":"2023","journal-title":"Transl. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"20190191","DOI":"10.1515\/jbcpp-2019-0191","article-title":"Tangeretin: A mechanistic review of its pharmacological and therapeutic effects","volume":"31","author":"Ashrafizadeh","year":"2020","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1093\/jpp\/rgab013","article-title":"Tangeretin as an adjuvant and chemotherapeutic sensitizer against various types of cancers: A comparative overview","volume":"73","author":"Alhamad","year":"2021","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.bbi.2009.02.013","article-title":"Bioactive components of tea: Cancer, inflammation and behavior","volume":"23","author":"Puangpraphant","year":"2009","journal-title":"Brain Behav. Immun."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Nauman, M.C., Won, J.H., Petiwala, S.M., Vemu, B., Lee, H., Sverdlov, M., and Johnson, J.J. (2023). alpha-Mangostin Promotes In Vitro and In Vivo Degradation of Androgen Receptor and AR-V7 Splice Variant in Prostate Cancer Cells. Cancers, 15.","DOI":"10.3390\/cancers15072118"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"113266","DOI":"10.1016\/j.biopha.2022.113266","article-title":"alpha-Terthienyl induces prostate cancer cell death through inhibiting androgen receptor expression","volume":"152","author":"Gan","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_94","first-page":"225","article-title":"The antiandrogenic effect of neferine, liensinine, and isoliensinine by inhibiting 5-alpha-reductase and androgen receptor expression via PI3K\/AKT signaling pathway in prostate cancer","volume":"76","author":"Liu","year":"2021","journal-title":"Pharmazie"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"11769351221118556","DOI":"10.1177\/11769351221118556","article-title":"Molecular Modeling Studies of Natural Inhibitors of Androgen Signaling in Prostate Cancer","volume":"21","author":"Olubode","year":"2022","journal-title":"Cancer Inform."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1002\/1878-0261.13637","article-title":"Manzamine A reduces androgen receptor transcription and synthesis by blocking E2F8-DNA interactions and effectively inhibits prostate tumor growth in mice","volume":"18","author":"Karan","year":"2024","journal-title":"Mol. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"100667","DOI":"10.1016\/j.phyplu.2024.100667","article-title":"Assessing the antiproliferative properties of various teas against the DU-145 prostate cancer cell line: A combined in vitro and in silico investigation","volume":"4","author":"Muriuki","year":"2024","journal-title":"Phytomed. Plus"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"408","DOI":"10.32768\/abc.2024114408-417","article-title":"Effects of Lupeol on Estrogen and Androgen Receptor-Positive Breast and Prostate Cancer Cells: Lupeol in ER+ and AR+ BC and PC cells","volume":"11","author":"Alizadeh","year":"2024","journal-title":"Arch. Breast Cancer"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Khan, H., Azad, I., Arif, Z., Nasibullah, M., Khan, M.F., and Arshad, M. (2025). Computational and biological insights for anti-cancer effects of Karanjin through AR\/ER modulation, ROS generation and cell cycle arrest in prostate cancer. J. Tradit. Complement. Med.","DOI":"10.1016\/j.jtcme.2025.03.008"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"101377","DOI":"10.1016\/j.imu.2023.101377","article-title":"An in silico study of bioactive compounds of Annona muricata in the design of ani-prostate cancer agent: MM\/GBSA, pharmacophore modeling and ADMET parameters","volume":"43","author":"Apeh","year":"2023","journal-title":"Inform. Med. Unlocked"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1016\/j.bmcl.2017.03.038","article-title":"Synthesis and biological evaluation of novel selective androgen receptor modulators (SARMs). Part II: Optimization of 4-(pyrrolidin-1-yl)benzonitrile derivatives","volume":"27","author":"Asano","year":"2017","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_102","first-page":"4025","article-title":"Targeting CWR22Rv1 Prostate Cancer Cell Proliferation and Gene Expression by Combinations of the Phytochemicals EGCG, Genistein and Quercetin","volume":"29","author":"Hsieh","year":"2009","journal-title":"Anticancer Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1093\/nar\/gkac1158","article-title":"Dynamic phase separation of the androgen receptor and its coactivators key to regulate gene expression","volume":"51","author":"Zhang","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Pungsrinont, T., Kallenbach, J., and Baniahmad, A. (2021). Role of PI3K-AKT-mTOR Pathway as a Pro-Survival Signaling and Resistance-Mediating Mechanism to Therapy of Prostate Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011088"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s10142-025-01526-z","article-title":"Role of long non-coding RNAs and natural products in prostate cancer: Insights into key signaling pathways","volume":"25","author":"Doghish","year":"2025","journal-title":"Funct. Integr. Genom."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clgc.2019.09.015","article-title":"Androgen Receptor Splice Variant, AR-V7, as a Biomarker of Resistance to Androgen Axis-Targeted Therapies in Advanced Prostate Cancer","volume":"18","author":"Zhang","year":"2020","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Zheng, Z., Li, J., Liu, Y., Shi, Z., Xuan, Z., Yang, K., Xu, C., Bai, Y., Fu, M., and Xiao, Q. (2022). The Crucial Role of AR-V7 in Enzalutamide-Resistance of Castration-Resistant Prostate Cancer. Cancers, 14.","DOI":"10.3390\/cancers14194877"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Rahman, M., Akter, K., Ahmed, K.R., Fahim, M.M., Aktary, N., Park, M.N., Shin, S.-W., and Kim, B. (2024). Synergistic Strategies for Castration-Resistant Prostate Cancer: Targeting AR-V7, Exploring Natural Compounds, and Optimizing FDA-Approved Therapies. Cancers, 16.","DOI":"10.3390\/cancers16162777"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"100937","DOI":"10.1016\/j.xcrm.2023.100937","article-title":"Harnessing transcriptionally driven chromosomal instability adaptation to target therapy-refractory lethal prostate cancer","volume":"4","author":"Dhital","year":"2023","journal-title":"Cell Rep. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"177295","DOI":"10.1016\/j.ejphar.2025.177295","article-title":"Manzamine A: A promising marine-derived cancer therapeutic for multi-targeted interactions with E2F8, SIX1, AR, GSK-3\u03b2, and V-ATPase-A systematic review","volume":"990","author":"Mishan","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"20886","DOI":"10.1021\/acsnano.4c05013","article-title":"Advanced Bioinspired Multifunctional Platforms Focusing on Gut Microbiota Regulation","volume":"18","author":"Li","year":"2024","journal-title":"ACS Nano"},{"key":"ref_112","first-page":"1934578X1701200337","article-title":"Phytoconstituents and Biological Activities of Garcinia Dulcis (Clusiaceae): A Review","volume":"12","author":"Khamthong","year":"2017","journal-title":"Nat. Prod. Commun."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1007\/s43450-023-00360-3","article-title":"Cannabidiol Negatively Regulates Androgenic Signal in Prostate Cancer Cells and Fine-Tunes the Tumorigenesis by Modulating Endoplasmic Reticulum-Associated Degradation, Unfolded Protein Response, and Autophagy","volume":"33","author":"Erzurumlu","year":"2023","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Shibata, M.-A., Iinuma, M., Morimoto, J., Kurose, H., Akamatsu, K., Okuno, Y., Akao, Y., and Otsuki, Y. (2011). \u03b1-Mangostin extracted from the pericarp of the mangosteen (Garcinia mangostana Linn) reduces tumor growth and lymph node metastasis in an immunocompetent xenograft model of metastatic mammary cancer carrying a p53 mutation. BMC Med., 9.","DOI":"10.1186\/1741-7015-9-69"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"7944","DOI":"10.1039\/D2CS00486K","article-title":"New opportunities for immunomodulation of the tumour microenvironment using chemical tools","volume":"51","author":"Su","year":"2022","journal-title":"Chem. Soc. Rev."},{"key":"ref_116","first-page":"53","article-title":"Cell signaling pathways altered by natural chemopreventive agents","volume":"555","author":"Sarkar","year":"2004","journal-title":"Mutat. Res. Fundam. Mol. Mech. Mutagen."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/s12672-015-0239-9","article-title":"Moving Beyond the Androgen Receptor (AR): Targeting AR-Interacting Proteins to Treat Prostate Cancer","volume":"7","author":"Foley","year":"2016","journal-title":"Horm. Cancer"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1586\/eem.11.33","article-title":"Outsmarting androgen receptor: Creative approaches for targeting aberrant androgen signaling in advanced prostate cancer","volume":"6","author":"Knudsen","year":"2011","journal-title":"Expert Rev. Endocrinol. Metab."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1210\/me.2002-0070","article-title":"The Roles of Androgen Receptors and Androgen-Binding Proteins in Nongenomic Androgen Actions","volume":"16","author":"Heinlein","year":"2002","journal-title":"Mol. Endocrinol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.steroids.2009.10.005","article-title":"An overview on 5\u03b1-reductase inhibitors","volume":"75","author":"Aggarwal","year":"2010","journal-title":"Steroids"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1089\/adt.2018.870","article-title":"Discovery of Natural Steroid 5 Alpha-Reductase Inhibitors","volume":"17","author":"Srivilai","year":"2019","journal-title":"ASSAY Drug Dev. Technol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"530121","DOI":"10.1155\/2012\/530121","article-title":"The 5 Alpha-Reductase Isozyme Family: A Review of Basic Biology and Their Role in Human Diseases","volume":"2012","author":"Azzouni","year":"2012","journal-title":"Adv. Urol."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Hasannejad-Asl, B., Pooresmaeil, F., Azadi, S., Najafi, A., Esmaeili, A., Bagheri-Mohammadi, S., and Kazemi, B. (2025). Computational drug discovery of potential 5\u03b1-reductase phytochemical inhibitors and hair growth promotion using in silico techniques. Front. Bioinform., 5.","DOI":"10.3389\/fbinf.2025.1570101"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1016\/j.jsps.2023.05.004","article-title":"Neferine attenuates development of testosterone-induced benign prostatic hyperplasia in mice by regulating androgen and TGF-\u03b2\/Smad signaling pathways","volume":"31","author":"Liu","year":"2023","journal-title":"Saudi Pharm. J."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1210\/en.2016-1926","article-title":"Inverse Regulation of DHT Synthesis Enzymes 5\u03b1-Reductase Types 1 and 2 by the Androgen Receptor in Prostate Cancer","volume":"158","author":"Yee","year":"2017","journal-title":"Endocrinology"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S1044-579X(02)00131-1","article-title":"Cell surface Death Receptor signaling in normal and cancer cells","volume":"13","year":"2003","journal-title":"Semin. Cancer Biol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.mce.2017.02.025","article-title":"Membrane androgen receptor characteristics of human ZIP9 (SLC39A) zinc transporter in prostate cancer cells: Androgen-specific activation and involvement of an inhibitory G protein in zinc and MAP kinase signaling","volume":"447","author":"Thomas","year":"2017","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.ygcen.2017.04.016","article-title":"ZIP9, a novel membrane androgen receptor and zinc transporter protein","volume":"257","author":"Thomas","year":"2018","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.steroids.2007.12.009","article-title":"Membrane-initiated steroid action in breast and prostate cancer","volume":"73","author":"Kampa","year":"2008","journal-title":"Steroids"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Moreira-Silva, F., Henrique, R., and Jer\u00f3nimo, C. (2022). From Therapy Resistance to Targeted Therapies in Prostate Cancer. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.877379"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Figueira, M.I., Carvalho, T.M.A., Mac\u00e1rio-Monteiro, J., Cardoso, H.J., Correia, S., Vaz, C.V., Duarte, A.P., and Socorro, S. (2024). The Pros and Cons of Estrogens in Prostate Cancer: An Update with a Focus on Phytoestrogens. Biomedicines, 12.","DOI":"10.3390\/biomedicines12081636"},{"key":"ref_132","unstructured":"Mahmoud, A.M. (2013). Androgen Receptor Mutations and Estrogen Receptor-\u03b2 Modulate Genistein Effects on Prostate Cancer Cells. [Ph.D. Thesis, University of Illinois at Chicago]."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"178","DOI":"10.4161\/cbt.6.2.3577","article-title":"Curcumin induces G2\/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by modulating Akt and p38 MAPK","volume":"6","author":"Weir","year":"2007","journal-title":"Cancer Biol. Ther."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Tubtimsri, S., Chuenbarn, T., and Manmuan, S. (2025). Quercetin triggers cell apoptosis-associated ROS-mediated cell death and induces S and G2\/M-phase cell cycle arrest in KON oral cancer cells. BMC Complement. Med. Ther., 25.","DOI":"10.1186\/s12906-025-04782-5"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.bbrc.2011.05.032","article-title":"Asperlin induces G2\/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells","volume":"409","author":"He","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Chuang, T.-C., Shao, W.-S., Hsu, S.-C., Lee, S.-L., Kao, M.-C., and Wang, V. (2023). Baicalein Induces G2\/M Cell Cycle Arrest Associated with ROS Generation and CHK2 Activation in Highly Invasive Human Ovarian Cancer Cells. Molecules, 28.","DOI":"10.3390\/molecules28031039"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.fct.2017.12.007","article-title":"Auriculasin-induced ROS causes prostate cancer cell death via induction of apoptosis","volume":"111","author":"Cho","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"3945","DOI":"10.1111\/cas.15068","article-title":"Reactive oxygen species in cancer: Current findings and future directions","volume":"112","author":"Nakamura","year":"2021","journal-title":"Cancer Sci."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"9659","DOI":"10.2147\/IJN.S479212","article-title":"Novel Strategies for Tumor Treatment: Harnessing ROS-Inducing Active Ingredients from Traditional Chinese Medicine Through Multifunctional Nanoformulations","volume":"19","author":"Zhang","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"100108","DOI":"10.1016\/j.cstres.2025.100108","article-title":"Reactive oxygen species in cancer: Mechanistic insights and therapeutic innovations","volume":"30","author":"Ma","year":"2025","journal-title":"Cell Stress Chaperones"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/s41585-023-00726-1","article-title":"Preclinical models of prostate cancer\u2014Modelling androgen dependency and castration resistance in vitro, ex vivo and in vivo","volume":"20","author":"Germain","year":"2023","journal-title":"Nat. Rev. Urol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/5\/786\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:15:59Z","timestamp":1772774159000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/5\/786"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,28]]},"references-count":141,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["cancers18050786"],"URL":"https:\/\/doi.org\/10.3390\/cancers18050786","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,28]]}}}