{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T06:31:06Z","timestamp":1778567466591,"version":"3.51.4"},"reference-count":93,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,29]],"date-time":"2023-05-29T00:00:00Z","timestamp":1685318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Catalysis S.L."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Prostate cancer is one of the most common cancers among men. Although many patients respond favorably to first-line treatments, castration\u2014and chemotherapy\u2014resistance arises after a few years, leading to metastasis. Thus, new approaches are being investigated using natural supplements to reinforce current therapies. Ocoxin is a plant-based mixture with antitumor properties that have been proved in several cancers. Here, we evaluated the cytotoxic capacity of this compound itself and combined with Docetaxel, Enzalutamide and Olaparib as an adjuvant agent. We observed that Ocoxin reduced tumor cell viability; slowed down cell cycles; altered the expression of genes involved in DNA replication, cell cycles and the p53 signaling pathway; and reduced migratory capacity after stimulation with cancer-associated fibroblasts (CAFs) and osteoblasts in vitro and reduced tumor volume in vivo. The combination of the nutritional supplement with chemotherapy showed a higher cytotoxic effect than chemotherapy alone and reverted chemoresistance conferred by CAFs and osteoblasts. Moreover, the adjuvant therapy also improved the outcome in vivo compared to the treatment with solo chemotherapy, where mice developed smaller tumors and less angiogenesis. Therefore, Ocoxin arises as a good candidate for further studies in combination with current treatments for prostate-cancer patients.<\/jats:p>","DOI":"10.3390\/nu15112536","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T02:04:21Z","timestamp":1685412261000},"page":"2536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Improving the Antitumor Effect of Chemotherapy with Ocoxin as a Novel Adjuvant Agent to Treat Prostate Cancer"],"prefix":"10.3390","volume":"15","author":[{"given":"Iera","family":"Hernandez-Unzueta","sequence":"first","affiliation":[{"name":"Cell Biology and Histology Department, Medicine and Nursing Faculty, University of the Basque Country, 48940 Leioa, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aitor","family":"Benedicto","sequence":"additional","affiliation":[{"name":"Cell Biology and Histology Department, Medicine and Nursing Faculty, University of the Basque Country, 48940 Leioa, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uxue","family":"Telleria","sequence":"additional","affiliation":[{"name":"Cell Biology and Histology Department, Medicine and Nursing Faculty, University of the Basque Country, 48940 Leioa, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Sanz","sequence":"additional","affiliation":[{"name":"Research and Development, Catalysis S.L., 28016 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6429-615X","authenticated-orcid":false,"given":"Joana","family":"M\u00e1rquez","sequence":"additional","affiliation":[{"name":"Cell Biology and Histology Department, Medicine and Nursing Faculty, University of the Basque Country, 48940 Leioa, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","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_2","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1001\/jama.2017.7248","article-title":"The Diagnosis and Treatment of Prostate Cancer: A Review","volume":"317","author":"Litwin","year":"2017","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3724","DOI":"10.18632\/oncotarget.12554","article-title":"Androgen receptor-dependent and -independent mechanisms driving prostate cancer progression: Opportunities for therapeutic targeting from multiple angles","volume":"8","author":"Hoang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1007\/s12325-016-0351-4","article-title":"An Update on Triptorelin: Current Thinking on Androgen Deprivation Therapy for Prostate Cancer","volume":"33","author":"Merseburger","year":"2016","journal-title":"Adv. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.neo.2020.09.002","article-title":"Development and prevalence of castration-resistant prostate cancer subtypes","volume":"22","author":"Vellky","year":"2020","journal-title":"Neoplasia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-319-95693-0_1","article-title":"Brief Overview of Prostate Cancer Statistics, Grading, Diagnosis and Treatment Strategies","volume":"1095","author":"Schatten","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1056\/NEJMoa1911440","article-title":"Olaparib for Metastatic Castration-Resistant Prostate Cancer","volume":"382","author":"Mateo","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.2217\/fon-2020-1245","article-title":"Olaparib for the treatment of metastatic prostate cancer","volume":"17","author":"Dror","year":"2021","journal-title":"Future Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1056\/NEJMoa1506859","article-title":"DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer","volume":"373","author":"Mateo","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1056\/NEJMoa2022485","article-title":"PROfound Trial Investigators Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer","volume":"383","author":"Hussain","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s11934-019-0924-2","article-title":"Quality of Life-Focused Decision-Making for Prostate Cancer","volume":"20","author":"Shevach","year":"2019","journal-title":"Curr. Urol. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/978-3-030-73119-9_16","article-title":"Current Treatment Modalities Targeting Tumor Microenvironment in Castration-Resistant Prostate Cancer","volume":"1329","author":"Nagireddy","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1373\/clinchem.2012.185363","article-title":"Targeting the tumor microenvironment for cancer therapy","volume":"59","author":"Sounni","year":"2013","journal-title":"Clin. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"14269","DOI":"10.1038\/s41598-018-32549-1","article-title":"Integrative metabolic and transcriptomic profiling of prostate cancer tissue containing reactive stroma","volume":"8","author":"Andersen","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.canlet.2015.12.022","article-title":"Regulation of prostate cancer progression by the tumor microenvironment","volume":"380","author":"Shiao","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/s41568-019-0238-1","article-title":"A framework for advancing our understanding of cancer-associated fibroblasts","volume":"20","author":"Sahai","year":"2020","journal-title":"Nat. Rev. Cancer."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S0140-6736(00)04046-0","article-title":"Inflammation and cancer: Back to Virchow?","volume":"357","author":"Balkwill","year":"2001","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/S0002-9440(10)64255-1","article-title":"Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis","volume":"161","author":"Schoppmann","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Martori, C., Sanchez-Moral, L., Paul, T., Pardo, J.C., Font, A., Ruiz de Porras, V., and Sarrias, M. (2022). Macrophages as a Therapeutic Target in Metastatic Prostate Cancer: A Way to Overcome Immunotherapy Resistance?. Cancers, 14.","DOI":"10.3390\/cancers14020440"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Han, I., Song, H., and Ryu, J. (2020). IL-6 produced by prostate epithelial cells stimulated with Trichomonas vaginalis promotes proliferation of prostate cancer cells by inducing M2 polarization of THP-1-derived macrophages. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008126"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1007\/s00018-018-2997-3","article-title":"Tumor-associated macrophages: A short compendium","volume":"76","author":"Prenen","year":"2019","journal-title":"Cell Mol. Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"119132","DOI":"10.1016\/j.lfs.2021.119132","article-title":"The role of regulatory T cells in the pathogenesis and treatment of prostate cancer","volume":"284","author":"Karpisheh","year":"2021","journal-title":"Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"T95","DOI":"10.1530\/ERC-21-0149","article-title":"The tumor microenvironment and immune responses in prostate cancer patients","volume":"28","author":"Kwon","year":"2021","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5399","DOI":"10.1158\/0008-5472.CAN-21-2708","article-title":"Macrophage Regulation of the Development of Castration-Resistant Prostate Cancer","volume":"81","author":"Lewis","year":"2021","journal-title":"Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1158\/0008-5472.CAN-19-2948","article-title":"Revisiting Immunotherapy: A Focus on Prostate Cancer","volume":"80","author":"Cha","year":"2020","journal-title":"Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3182","DOI":"10.1158\/1078-0432.CCR-19-3372","article-title":"T-Cell Infiltration and Adaptive Treg Resistance in Response to Androgen Deprivation with or Without Vaccination in Localized Prostate Cancer","volume":"26","author":"Obradovic","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.canlet.2021.10.027","article-title":"The evolving role of immune cells in prostate cancer","volume":"525","author":"Wang","year":"2022","journal-title":"Cancer Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.ccell.2020.06.005","article-title":"Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer","volume":"38","author":"Zhang","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.bone.2014.06.023","article-title":"Modifying the osteoblastic niche with zoledronic acid in vivo-potential implications for breast cancer bone metastasis","volume":"66","author":"Haider","year":"2014","journal-title":"Bone"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.urology.2015.12.039","article-title":"Biology of Bone Metastases in Prostate Cancer","volume":"92","author":"Hensel","year":"2016","journal-title":"Urology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nature17038","article-title":"Metastatic colonization by circulating tumour cells","volume":"529","author":"Obenauf","year":"2016","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"738235","DOI":"10.3389\/fphar.2021.738235","article-title":"Molecular Basis of Prostate Cancer and Natural Products as Potential Chemotherapeutic and Chemopreventive Agents","volume":"12","author":"Bai","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Crocetto, F., di Zazzo, E., Buonerba, C., Aveta, A., Pandolfo, S.D., Barone, B., Trama, F., Caputo, V.F., Scafuri, L., and Ferro, M. (2021). Kaempferol, Myricetin and Fisetin in Prostate and Bladder Cancer: A Systematic Review of the Literature. Nutrients, 13.","DOI":"10.3390\/nu13113750"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Salehi, B., Fokou, P.V.T., Yamthe, L.R.T., Tali, B.T., Adetunji, C.O., Rahavian, A., Mudau, F.N., Martorell, M., Setzer, W.N., and Rodrigues, C.F. (2019). Phytochemicals in Prostate Cancer: From Bioactive Molecules to Upcoming Therapeutic Agents. Nutrients, 11.","DOI":"10.3390\/nu11071483"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sekhoacha, M., Riet, K., Motloung, P., Gumenku, L., Adegoke, A., and Mashele, S. (2022). Prostate Cancer Review: Genetics, Diagnosis, Treatment Options, and Alternative Approaches. Molecules, 27.","DOI":"10.3390\/molecules27175730"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wang, X., Fang, G., and Pang, Y. (2018). Chinese Medicines in the Treatment of Prostate Cancer: From Formulas to Extracts and Compounds. Nutrients, 10.","DOI":"10.3390\/nu10030283"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3390\/jox11010002","article-title":"The Effects of Resveratrol on Prostate Cancer through Targeting the Tumor Microenvironment","volume":"11","author":"Silk","year":"2021","journal-title":"J. Xenobiot."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Pietrovito, L., Iozzo, M., Bacci, M., Giannoni, E., and Chiarugi, P. (2020). Treatment with Cannabinoids as a Promising Approach for Impairing Fibroblast Activation and Prostate Cancer Progression. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030787"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ma, J., Chen, X., Chen, Y., Tao, N., and Qin, Z. (2022). Ligustilide Inhibits Tumor Angiogenesis by Downregulating VEGFA Secretion from Cancer-Associated Fibroblasts in Prostate Cancer via TLR4. Cancers, 14.","DOI":"10.3390\/cancers14102406"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1002\/jcb.21500","article-title":"Targeting cell signaling pathways for drug discovery: An old lock needs a new key","volume":"102","author":"Aggarwal","year":"2007","journal-title":"J. Cell. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2310\/7200.2006.029","article-title":"From ancient medicine to modern medicine: Ayurvedic concepts of health and their role in inflammation and cancer","volume":"5","author":"Garodia","year":"2007","journal-title":"J. Soc. Integr. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1080\/01635581.2011.523502","article-title":"Targeting cell signaling and apoptotic pathways by dietary agents: Role in the prevention and treatment of cancer","volume":"63","author":"Shanmugam","year":"2011","journal-title":"Nutr. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.clnu.2013.03.008","article-title":"Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy","volume":"32","author":"Lecumberri","year":"2013","journal-title":"Clin. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"113610","DOI":"10.1016\/j.biopha.2022.113610","article-title":"Natural products as chemo-radiation therapy sensitizers in cancers","volume":"154","author":"Nisar","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"745177","DOI":"10.3389\/fcell.2021.745177","article-title":"Natural Products for the Management of Castration-Resistant Prostate Cancer: Special Focus on Nanoparticles Based Studies","volume":"9","author":"Singla","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Wang, K., Yu, Y., Chen, H., Chiang, Y., Ali, M., Shieh, T., and Hsia, S. (2022). Recent Advances in Glycyrrhiza glabra (Licorice)-Containing Herbs Alleviating Radiotherapy- and Chemotherapy-Induced Adverse Reactions in Cancer Treatment. Metabolites, 12.","DOI":"10.3390\/metabo12060535"},{"key":"ref_47","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_48","doi-asserted-by":"crossref","unstructured":"Benedicto, A., Hernandez-Unzueta, I., Sanz, E., and M\u00e1rquez, J. (2021). Ocoxin Increases the Antitumor Effect of BRAF Inhibition and Reduces Cancer Associated Fibroblast-Mediated Chemoresistance and Protumoral Activity in Metastatic Melanoma. Nutrients, 13.","DOI":"10.3390\/nu13020686"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4002","DOI":"10.3892\/ol.2017.6016","article-title":"Ocoxin oral solution(\u00ae) as a complement to irinotecan chemotherapy in the metastatic progression of colorectal cancer to the liver","volume":"13","author":"Benedicto","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1097\/MPA.0000000000001277","article-title":"Ocoxin Oral Solution Exerts an Antitumoral Effect in Pancreatic Cancer and Reduces the Stromal-Mediated Chemoresistance","volume":"48","author":"Benedicto","year":"2019","journal-title":"Pancreas"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.3892\/or.2015.4486","article-title":"Ocoxin\u00ae oral solution slows down tumor growth in an experimental model of colorectal cancer metastasis to the liver in Balb\/c mice","volume":"35","author":"Mena","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_52","first-page":"1387","article-title":"Glycyrrhizin induces apoptosis in prostate cancer cell lines DU-145 and LNCaP","volume":"20","author":"Thirugnanam","year":"2008","journal-title":"Oncol. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Shirakami, Y., and Shimizu, M. (2018). Possible Mechanisms of Green Tea and Its Constituents against Cancer. Molecules, 23.","DOI":"10.3390\/molecules23092284"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ejmech.2019.05.067","article-title":"Anti-cancer effects of cinnamon: Insights into its apoptosis effects","volume":"178","author":"Sadeghi","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"D587","DOI":"10.1093\/nar\/gkac963","article-title":"KEGG for taxonomy-based analysis of pathways and genomes","volume":"51","author":"Kanehisa","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"443","DOI":"10.4103\/0019-509X.176699","article-title":"Increased survival of patients with end-stage hepatocellular carcinoma due to intake of ONCOXIN\u00ae, a dietary supplement","volume":"52","author":"Akbar","year":"2015","journal-title":"Indian J. Cancer"},{"key":"ref_57","first-page":"5644","article-title":"Multicomponent nutritional supplement Oncoxin and its influence on quality of life and therapy toxicity in patients receiving adjuvant chemotherapy","volume":"18","author":"Kaidarova","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"276","DOI":"10.4236\/jct.2020.115023","article-title":"Efficacy of Oncoxin-Viusid on the Reduction of Adverse Reactions to Chemotherapy and Radiotherapy in Patients Diagnosed with Cervical Cancer and Endometrial Adenocarcinoma","volume":"11","year":"2020","journal-title":"J. Cancer Ther."},{"key":"ref_59","first-page":"463","article-title":"Oncoxin nutritional supplement in the management of chemotherapy- and\/or radiotherapy-associated oral mucositis","volume":"10","author":"Shumsky","year":"2019","journal-title":"Mol. Clin. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/pro.4172","article-title":"KEGG mapping tools for uncovering hidden features in biological data","volume":"31","author":"Kanehisa","year":"2022","journal-title":"Protein Sci."},{"key":"ref_61","first-page":"306","article-title":"Advanced prostate cancer and quality of life","volume":"71","year":"2018","journal-title":"Arch. Esp. Urol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Fontana, F., Raimondi, M., Marzagalli, M., Di Domizio, A., and Limonta, P. (2020). Natural Compounds in Prostate Cancer Prevention and Treatment: Mechanisms of Action and Molecular Targets. Cells, 9.","DOI":"10.3390\/cells9020460"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Termini, D., Den Hartogh, D.J., Jaglanian, A., and Tsiani, E. (2020). Curcumin against Prostate Cancer: Current Evidence. Biomolecules, 10.","DOI":"10.3390\/biom10111536"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.canlet.2012.05.012","article-title":"Green tea: An effective synergist with anticancer drugs for tertiary cancer prevention","volume":"324","author":"Fujiki","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"245","DOI":"10.3109\/19390211.2015.1008614","article-title":"Emerging Adjuvant Therapy for Cancer: Propolis and its Constituents","volume":"13","author":"Patel","year":"2016","journal-title":"J. Diet. Suppl."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s12935-019-0769-2","article-title":"Combination of the natural product capsaicin and docetaxel synergistically kills human prostate cancer cells through the metabolic regulator AMP-activated kinase","volume":"19","author":"Bort","year":"2019","journal-title":"Cancer. Cell. Int."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2770","DOI":"10.1158\/1535-7163.MCT-17-0030","article-title":"Quercetin Targets hnRNPA1 to Overcome Enzalutamide Resistance in Prostate Cancer Cells","volume":"16","author":"Tummala","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.jnutbio.2014.11.017","article-title":"Sensitization to docetaxel in prostate cancer cells by green tea and quercetin","volume":"26","author":"Wang","year":"2015","journal-title":"J. Nutr. Biochem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4201","DOI":"10.2174\/1381612822666160601100823","article-title":"Phytochemicals as Adjunctive with Conventional Anticancer Therapies","volume":"22","author":"Farzaei","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"16","DOI":"10.5582\/bst.2015.01019","article-title":"The advantages of using traditional Chinese medicine as an adjunctive therapy in the whole course of cancer treatment instead of only terminal stage of cancer","volume":"9","author":"Qi","year":"2015","journal-title":"Biosci. Trends"},{"key":"ref_71","first-page":"5","article-title":"Oncoxin-Viusid(\u00ae) may improve quality of life and survival in patients with hormone-refractory prostate cancer undergoing onco-specific treatments","volume":"14","author":"Maden","year":"2021","journal-title":"Mol. Clin. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"8978731","DOI":"10.1155\/2018\/8978731","article-title":"Cinnamon in Anticancer Armamentarium: A Molecular Approach","volume":"2018","author":"Dutta","year":"2018","journal-title":"J. Toxicol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Pandiella-Alonso, A., D\u00edaz-Rodr\u00edguez, E., and Sanz, E. (2020). Antitumoral Properties of the Nutritional Supplement Ocoxin Oral Solution: A Comprehensive Review. Nutrients, 12.","DOI":"10.3390\/nu12092661"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6437","DOI":"10.7314\/APJCP.2014.15.15.6437","article-title":"Downregulation of Cdk1 and cyclinB1 expression contributes to oridonin-induced cell cycle arrest at G2\/M phase and growth inhibition in SGC-7901 gastric cancer cells","volume":"15","author":"Gao","year":"2014","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_75","first-page":"66","article-title":"MicroRNA-188 suppresses G1\/S transition by targeting multiple cyclin\/CDK complexes","volume":"12","author":"Wu","year":"2014","journal-title":"Cell. Commun. Signal."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.pep.2009.02.007","article-title":"Differential phosphorylation patterns between the Cyclin-A2\/CDK2 complex and their monomers","volume":"66","author":"Casal","year":"2009","journal-title":"Protein Expr. Purif."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"23681","DOI":"10.1038\/s41598-021-03166-2","article-title":"Tanshinone IIA suppresses the progression of lung adenocarcinoma through regulating CCNA2-CDK2 complex and AURKA\/PLK1 pathway","volume":"11","author":"Li","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1038\/s41467-021-22327-5","article-title":"Dominant role of CDKN2B\/p15INK4B of 9p21.3 tumor suppressor hub in inhibition of cell-cycle and glycolysis","volume":"12","author":"Xia","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"110052","DOI":"10.18632\/oncotarget.22123","article-title":"CDKN2B is critical for verapamil-mediated reversal of doxorubicin resistance in hepatocellular carcinoma","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1593\/tlo.10286","article-title":"Synergistic Effects of the Green Tea Extract Epigallocatechin-3-gallate and Taxane in Eradication of Malignant Human Prostate Tumors","volume":"4","author":"Stearns","year":"2011","journal-title":"Transl. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A review of programmed cell death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1111\/jpi.12264","article-title":"Melatonin and endoplasmic reticulum stress: Relation to autophagy and apoptosis","volume":"59","author":"Reiter","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1111\/febs.13598","article-title":"Cell death induced by endoplasmic reticulum stress","volume":"283","author":"Iurlaro","year":"2016","journal-title":"FEBS J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"26908","DOI":"10.1074\/jbc.M110.132597","article-title":"MDM2 mediates ubiquitination and degradation of activating transcription factor 3","volume":"285","author":"Mo","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1038\/sj.emboj.7600712","article-title":"Activating transcription factor 3, a stress sensor, activates p53 by blocking its ubiquitination","volume":"24","author":"Yan","year":"2005","journal-title":"EMBO J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1080\/15548627.2020.1761651","article-title":"The anti-cancer drug ABTL0812 induces ER stress-mediated cytotoxic autophagy by increasing dihydroceramide levels in cancer cells","volume":"17","author":"Casas","year":"2021","journal-title":"Autophagy"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4542","DOI":"10.4161\/cc.9.22.13790","article-title":"Inhibition of Cot1\/Tlp2 oncogene in AML cells reduces ERK5 activation and up-regulates p27Kip1 concomitant with enhancement of differentiation and cell cycle arrest induced by silibinin and 1,25-dihydroxyvitamin D(3)","volume":"9","author":"Wang","year":"2010","journal-title":"Cell. Cycle"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.4161\/auto.24632","article-title":"Salinomycin induces cell death with autophagy through activation of endoplasmic reticulum stress in human cancer cells","volume":"9","author":"Li","year":"2013","journal-title":"Autophagy"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1158\/0008-5472.CAN-09-3537","article-title":"Resveratrol promotes autophagic cell death in chronic myelogenous leukemia cells via JNK-mediated p62\/SQSTM1 expression and AMPK activation","volume":"70","author":"Puissant","year":"2010","journal-title":"Cancer Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1172\/JCI37948","article-title":"Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells","volume":"119","author":"Salazar","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1007\/s11914-018-0480-6","article-title":"Osteoblastic Factors in Prostate Cancer Bone Metastasis","volume":"16","author":"Lin","year":"2018","journal-title":"Curr. Osteoporos Rep."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1002\/jbmr.2300","article-title":"Prostate cancer cells preferentially home to osteoblast-rich areas in the early stages of bone metastasis: Evidence from in vivo models","volume":"29","author":"Wang","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"110991","DOI":"10.1016\/j.fct.2019.110991","article-title":"Ligustilide promotes apoptosis of cancer-associated fibroblasts via the TLR4 pathways","volume":"135","author":"Ma","year":"2020","journal-title":"Food Chem. Toxicol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/11\/2536\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:44:41Z","timestamp":1760125481000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/11\/2536"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,29]]},"references-count":93,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["nu15112536"],"URL":"https:\/\/doi.org\/10.3390\/nu15112536","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,29]]}}}