{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:02:56Z","timestamp":1785402176444,"version":"3.56.0"},"reference-count":57,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"crossref","award":["791262"],"award-info":[{"award-number":["791262"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"crossref"}]},{"award":["791262"],"award-info":[{"award-number":["791262"]}],"id":[{"id":"https:\/\/ror.org\/059ex5q34","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cancer cells resort to metabolic reprogramming to sustain proliferation. Lung cancer has one of the highest mortality rates of all types of cancer. An important factor in its high mortality rate is its tumors\u2019 ability to undergo significant metabolic reprogramming. Phytochemicals can counteract this altered metabolism and exhibit anticancer properties. Coleus hadiensis, a plant used in traditional medicine, has shown such potential. This study evaluated the in vitro cytotoxic activity of its methanolic extract and its effects on the metabolism of HTB-177 lung cancer cells. Qualitative and quantitative phytochemical analysis of this extract was performed to characterize its main constituents. Lung cancer cells were treated with different extract concentrations to evaluate their response to the extract. Cytotoxicity was determined using an MTT assay, and metabolites were analyzed through 1H-NMR spectroscopy combined with multivariate statistical analysis. Transcriptomic profiling was also conducted to assess gene expression changes in metabolic pathways. Three main phenolic compounds were identified in the extract. The HPLC profile revealed peaks corresponding to gallic acid (GA), ferulic acid (FA), and rosmarinic acid (RA). The extract exhibited cytotoxic activity with an IC50 of 192.85 \u00b5g\/mL. Metabolic alterations were observed mainly in glycolysis, the Krebs cycle, and lipid metabolism\u2014key pathways for tumor growth. Transcriptomic data revealed altered metabolism-related genes. The upregulation of ME1 correlated with the observed increase in pyruvate levels, while the downregulation of ALDH7A1 and ASRGL1 was linked to altered amino acid catabolism. Furthermore, transcriptomic data revealed the upregulation of the pro-apoptotic gene HRK. These results indicate that the methanolic extract of C. hadiensis possesses cytotoxic activity against lung cancer cells by modulating central metabolic routes and gene expression linked to cancer cell survival and proliferation.<\/jats:p>","DOI":"10.3390\/molecules31071074","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:11:14Z","timestamp":1774429874000},"page":"1074","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Vitro Cytotoxic Activity of Coleus hadiensis Methanolic Extract: Metabolic and Transcriptomic Effects in Lung Cancer Cell Line"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2598-3317","authenticated-orcid":false,"given":"Ana L.","family":"Valdez-Arellanes","sequence":"first","affiliation":[{"name":"Laboratorio de Metabolismo Celular, Centro de Laboratorios Especializados (CELAES), Facultad de Ciencias Qu\u00edmicas, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Ciudad Universitaria, Pedro de Alba S\/N, San Nicol\u00e1s de los Garza 66451, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica A.","family":"Ram\u00edrez-Cabrera","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda Molecular y Modelos Biol\u00f3gicos, Facultad de Ciencias Qu\u00edmicas, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Vicente Guerrero s\/n, Col. Trevi\u00f1o, Monterrey 64570, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0983-7558","authenticated-orcid":false,"given":"Eder U.","family":"Arredondo-Espinoza","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda Molecular y Modelos Biol\u00f3gicos, Facultad de Ciencias Qu\u00edmicas, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Vicente Guerrero s\/n, Col. Trevi\u00f1o, Monterrey 64570, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7467-7538","authenticated-orcid":false,"given":"Emanuel","family":"Hern\u00e1ndez-N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Departamento de Posgrado e Investigaci\u00f3n, Instituto Tecnol\u00f3gico Superior de Calkin\u00ed, Av. Ah Canul S\/N por Carretera Federal, Calkin\u00ed 24930, Campeche, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4667-2972","authenticated-orcid":false,"given":"Monica N.","family":"Sanchez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Facultad de Ingenier\u00eda Qu\u00edmica, Campus de Ciencias Exactas e Ingenier\u00edas, Universidad Aut\u00f3noma de Yucat\u00e1n, Colonia Chuburn\u00e1 de Hidalgo Inn, Perif\u00e9rico Norte Km. 33.5, Tablaje Catastral 13615, M\u00e9rida 97203, Yucat\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5428-393X","authenticated-orcid":false,"given":"Isaias","family":"Balderas-Renter\u00eda","sequence":"additional","affiliation":[{"name":"Laboratorio de Metabolismo Celular, Centro de Laboratorios Especializados (CELAES), Facultad de Ciencias Qu\u00edmicas, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Ciudad Universitaria, Pedro de Alba S\/N, San Nicol\u00e1s de los Garza 66451, Nuevo Le\u00f3n, Mexico"},{"name":"Laboratorio de Farmacolog\u00eda Molecular y Modelos Biol\u00f3gicos, Facultad de Ciencias Qu\u00edmicas, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Vicente Guerrero s\/n, Col. Trevi\u00f1o, Monterrey 64570, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7840-7981","authenticated-orcid":false,"given":"Karla","family":"Ramirez-Estrada","sequence":"additional","affiliation":[{"name":"Laboratorio de Metabolismo Celular, Centro de Laboratorios Especializados (CELAES), Facultad de Ciencias Qu\u00edmicas, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Ciudad Universitaria, Pedro de Alba S\/N, San Nicol\u00e1s de los Garza 66451, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.7150\/jca.31406","article-title":"The Molecular Mechanism of Metabolic Remodeling in Lung Cancer","volume":"11","author":"Chang","year":"2020","journal-title":"J. Cancer"},{"key":"ref_3","unstructured":"Bast, R.C., Croce, C.M., Hait, W.N., Hong, W.K., Kufe, D.W., Piccart-Gebhart, M.J., Pollock, R.E., Weichselbaum, R.R., Wang, H., and Holland, J.F. (2017). Biological Hallmarks of Cancer, Wiley-Blackwell."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Khan, A., Siddiqui, S., Husain, S., Mazurek, S., Askandar Iqbal, M., Husain, S.A., and Iqbal, M.A. (2020). Phytochemicals Targeting Metabolic Reprogramming in Cancer: An Assessment of Role, Mechanisms, Pathways and Therapeutic Relevance. Authorea Preprints.","DOI":"10.22541\/au.160684227.70170021\/v1"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Shuvalov, O., Kirdeeva, Y., Daks, A., Fedorova, O., Parfenyev, S., Simon, H.U., and Barlev, N.A. (2023). Phytochemicals Target Multiple Metabolic Pathways in Cancer. Antioxidants, 12.","DOI":"10.3390\/antiox12112012"},{"key":"ref_6","first-page":"1","article-title":"Medicinal Plants for Treatment of Prevalent Diseases","volume":"17","author":"Archer","year":"2019","journal-title":"Pharmacogn. Med. Plants"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jep.2005.09.011","article-title":"Plectranthus: A Review of Ethnobotanical Uses","volume":"103","author":"Lukhoba","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13765-019-0464-y","article-title":"Low-Density Lipoprotein-Antioxidant Flavonoids and a Phenolic Ester from Plectranthus hadiensis Var. Tomentosus","volume":"62","author":"Ji","year":"2019","journal-title":"Appl. Biol. Chem."},{"key":"ref_9","first-page":"275","article-title":"Anti Inflammtory and Cytotoxic Activity of Methanolic Extract of Plectranthus hadiensis Stem","volume":"3","author":"Menon","year":"2011","journal-title":"Pharmacologyonline"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1080\/01635581.2015.1019631","article-title":"Terpenoids Isolated from the Shoot of Plectranthus hadiensis Induces Apoptosis in Human Colon Cancer Cells via the Mitochondria-Dependent Pathway","volume":"67","author":"Menon","year":"2015","journal-title":"Nutr. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Chen, Y., Gao, Y., Yi, X., Zhang, J., Chen, Z., and Wu, Y. (2020). Integration of Transcriptomics and Metabolomics Reveals the Antitumor Mechanism Underlying Shikonin in Colon Cancer. Front. Earth Sci., 11.","DOI":"10.3389\/fphar.2020.544647"},{"key":"ref_12","first-page":"300","article-title":"Pharmacognostic Study and Phytochemical Investigation of Plectranthus hadiensis","volume":"3","author":"Menon","year":"2011","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"ref_13","first-page":"457","article-title":"Chemical Investigations and the Antimicrobial Activity of Ocimum hadiensis (Forssk) Plant Grown Wild in Egypt","volume":"10","author":"Ibrahim","year":"2019","journal-title":"J. Mater. Environ. Sci"},{"key":"ref_14","first-page":"2297","article-title":"Assessment of Rosmarinic Acid Content in Six Lamiaceae Species Extracts and Their Antioxidant and Antimicrobial Potential","volume":"28","author":"Benedec","year":"2015","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"856","DOI":"10.3923\/ijp.2018.856.865","article-title":"Phenolic Acids and Biological Activities of Coleus Forskohlii and Plectranthus Barbatus as Traditional Medicinal Plants","volume":"14","author":"Ganash","year":"2018","journal-title":"Int. J. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Nadeem, M., Imran, M., Gondal, T.A., Imran, A., Shahbaz, M., Amir, R.M., Sajid, M.W., Qaisrani, T.B., Atif, M., and Hussain, G. (2019). Therapeutic Potential of Rosmarinic Acid: A Comprehensive Review. Appl. Sci., 9.","DOI":"10.3390\/app9153139"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"10300","DOI":"10.1038\/s41598-020-65648-z","article-title":"Rosmarinic Acid Exhibits Anticancer Effects via MARK4 Inhibition","volume":"10","author":"Anwar","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.fitote.2008.06.007","article-title":"Cytotoxic Activity Screening of Some Indigenous Thai Plants","volume":"79","author":"Prayong","year":"2008","journal-title":"Fitoterapia"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Guerra, \u00c2.R., Paulino, A.F., Castro, M.M., Oliveira, H., Duarte, M.F., and Duarte, I.F. (2020). Triple Negative Breast Cancer and Breast Epithelial Cells Differentially Reprogram Glucose and Lipid Metabolism upon Treatment with Triterpenic Acids. Biomolecules, 10.","DOI":"10.3390\/biom10081163"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/mc.23365","article-title":"Triterpenoid Ursolic Acid Drives Metabolic Rewiring and Epigenetic Reprogramming in Treatment\/Prevention of Human Prostate Cancer","volume":"61","author":"Li","year":"2021","journal-title":"Mol. Carcinog."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s11306-018-1376-2","article-title":"A Review of Metabolism-Associated Biomarkers in Lung Cancer Diagnosis and Treatment","volume":"14","author":"Miller","year":"2018","journal-title":"Metabolomics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1158\/0008-5472.CAN-15-2298","article-title":"Accumulated Metabolites of Hydroxybutyric Acid Serve as Diagnostic and Prognostic Biomarkers of Ovarian High-Grade Serous Carcinomas","volume":"76","author":"Hilvo","year":"2016","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mierziak, J., Burgberger, M., and Wojtasik, W. (2021). 3-Hydroxybutyrate as a Metabolite and a Signal Molecule Regulating Processes of Living Organisms. Biomolecules, 11.","DOI":"10.3390\/biom11030402"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.tcb.2019.05.005","article-title":"Acetate Metabolism in Physiology, Cancer, and Beyond","volume":"29","author":"Bose","year":"2019","journal-title":"Trends Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Weber, G.F. (2016). Time and Circumstances: Cancer Cell Metabolism at Various Stages of Disease Progression. Front. Oncol., 6.","DOI":"10.3389\/fonc.2016.00257"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1097\/CCO.0b013e328356da72","article-title":"Glucose Transporters in Cancer Metabolism HHS Public Access","volume":"24","author":"Adekola","year":"2012","journal-title":"Curr. Opin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Li, Q., Huang, Z., Li, B., Nice, E.C., Huang, C., Wei, L., and Zou, B. (2022). Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies. Cancers, 14.","DOI":"10.3390\/cancers14194568"},{"key":"ref_28","first-page":"2695","article-title":"Anti-Warburg Effect of Rosmarinic Acid via MiR-155 in Gastric Cancer Cells","volume":"9","author":"Han","year":"2015","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_29","first-page":"3","article-title":"Extracellular Citrate and Metabolic Adaptations of Cancer Cells","volume":"1","author":"Parkinson","year":"2021","journal-title":"Cancer Metastasis Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1002\/1878-0261.12369","article-title":"Metabolomic Profiling of Human Lung Tumor Tissues\u2014Nucleotide Metabolism as a Candidate for Therapeutic Interventions and Biomarkers","volume":"12","author":"Moreno","year":"2018","journal-title":"Mol. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Casas-Benito, A., Mart\u00ednez-Herrero, S., and Mart\u00ednez, A. (2023). Succinate-Directed Approaches for Warburg Effect-Targeted Cancer Management, an Alternative to Current Treatments?. Cancers, 15.","DOI":"10.3390\/cancers15102862"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/978-3-030-65768-0_2","article-title":"Glutamine Metabolism in Cancer","volume":"1311","author":"Li","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_33","first-page":"443","article-title":"Malonate Metabolism: Biochemistry, Molecular Biology, Physiology, and Industrial Application","volume":"35","author":"Yu","year":"2002","journal-title":"J. Biochem. Mol. Biol."},{"key":"ref_34","first-page":"283","article-title":"Specific Alterations in the Serum Amino Acid Profile of Patients with Lung Cancer and Head and Neck Cancer","volume":"29","author":"Dols","year":"2006","journal-title":"Oncologia"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1010428317694545","DOI":"10.1177\/1010428317694545","article-title":"Inhibition of L-Type Amino Acid Transporter 1 Activity as a New Therapeutic Target for Cholangiocarcinoma Treatment","volume":"39","author":"Yothaisong","year":"2017","journal-title":"Tumour Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"12904","DOI":"10.18632\/oncotarget.7354","article-title":"Serum Metabolomic Profiling Facilitates the Non-Invasive Identification of Metabolic Biomarkers Associated with the Onset and Progression of Non-Small Cell Lung Cancer","volume":"7","author":"Lucas","year":"2016","journal-title":"Oncotarget"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Yu, S., Yan, J., Yang, Z., Zhao, Y., Wang, H., and Yang, X. (2022). Metabolic Responses and Pathway Changes of Vero Cells under High-Vitamin B Medium. Vaccines, 10.","DOI":"10.3390\/vaccines10111787"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"D672","DOI":"10.1093\/nar\/gkae909","article-title":"KEGG: Biological Systems Database as a Model of the Real World","volume":"53","author":"Kanehisa","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"W216","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: A Web Server for Functional Enrichment Analysis and Functional Annotation of Gene Lists (2021 Update)","volume":"50","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"E1354","DOI":"10.1152\/ajpendo.90836.2008","article-title":"Role for Malic Enzyme, Pyruvate Carboxylation, and Mitochondrial Malate Import in Glucose-Stimulated Insulin Secretion","volume":"296","author":"Heart","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1158\/0008-5472.CAN-17-3155","article-title":"ME1 Regulates NADPH Homeostasis to Promote Gastric Cancer Growth and Metastasis","volume":"78","author":"Lu","year":"2018","journal-title":"Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"L\u00f3pez, V., Tejedor, J.R., Carella, A., Garc\u00eda, M.G., Santamarina-Ojeda, P., P\u00e9rez, R.F., Mangas, C., Urdinguio, R.G., Aranburu, A., and de la Nava, D. (2021). Epigenetic Deregulation of the Histone Methyltransferase KMT5B Contributes to Malignant Transformation in Glioblastoma. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.671838"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1083\/jcb.201901033","article-title":"Saccharopine, a Lysine Degradation Intermediate, Is a Mitochondrial Toxin","volume":"218","author":"Leandro","year":"2019","journal-title":"J. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1016\/j.gendis.2022.10.028","article-title":"Lysine Succinylation, the Metabolic Bridge between Cancer and Immunity","volume":"10","author":"Shen","year":"2022","journal-title":"Genes Dis."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Andrejeva, D., Kugler, J.M., Nguyen, H.T., Malmendal, A., Holm, M.L., Toft, B.G., Loya, A.C., and Cohen, S.M. (2018). Metabolic Control of PPAR Activity by Aldehyde Dehydrogenase Regulates Invasive Cell Behavior and Predicts Survival in Hepatocellular and Renal Clear Cell Carcinoma. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-5061-7"},{"key":"ref_46","first-page":"931","article-title":"RNAi-Mediated Downregulation of Asparaginase-like Protein 1 Inhibits Growth and Promotes Apoptosis of Human Cervical Cancer Line SiHa","volume":"18","author":"Lv","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.dld.2022.12.003","article-title":"ASRGL1 Downregulation Suppresses Hepatocellular Carcinoma Tumorigenesis in a CDK1-Dependent Manner","volume":"55","author":"Wang","year":"2023","journal-title":"Dig. Liver Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1007\/s12094-024-03431-6","article-title":"Integrated Analysis Reveals an Aspartate Metabolism-Related Gene Signature for Predicting the Overall Survival in Patients with Hepatocellular Carcinoma","volume":"26","author":"Shi","year":"2024","journal-title":"Clin. Transl. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"S105","DOI":"10.1038\/onc.2009.48","article-title":"The Role of HRK Gene in Human Cancer","volume":"27","author":"Nakamura","year":"2008","journal-title":"Oncogene"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"173419","DOI":"10.1016\/j.ejphar.2020.173419","article-title":"Rosmarinic Acid-Induced Apoptosis and Cell Cycle Arrest in Triple-Negative Breast Cancer Cells","volume":"885","author":"Messeha","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.31557\/APJCP.2023.24.7.2473","article-title":"Induction of Apoptosis and Modulation of Caspase Activity on MCF-7 Human Breast Cancer Cells by Bioactive Fractionated Cocoa Leaf Extract","volume":"24","author":"Ranneh","year":"2023","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Marada, A., Korupalli, C., Zhao, W., Xia, Y., Gao, Z., Chen, J., and Zhang, E. (2025). Multiple Roles of ALDH1 in Health and Disease. Front. Physiol., 16.","DOI":"10.3389\/fphys.2025.1627164"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1124\/dmd.110.034678","article-title":"Aldehyde Dehydrogenase 1B1: Molecular Cloning and Characterization of a Novel Mitochondrial Acetaldehyde-Metabolizing Enzyme","volume":"38","author":"Stagos","year":"2010","journal-title":"Drug Metab. Dispos."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1007\/s00726-021-02999-5","article-title":"Structure, Biochemistry, and Gene Expression Patterns of the Proline Biosynthetic Enzyme Pyrroline-5-Carboxylate Reductase (PYCR), an Emerging Cancer Therapy Target","volume":"53","author":"Bogner","year":"2021","journal-title":"Amino Acids"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"18846","DOI":"10.1038\/srep18846","article-title":"PYCR1 and PYCR2 Interact and Collaborate with RRM2B to Protect Cells from Overt Oxidative Stress","volume":"6","author":"Kuo","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1007\/s00726-021-03103-7","article-title":"Perspectives, Past, Present and Future: The Proline Cycle\/Proline-Collagen Regulatory Axis","volume":"53","author":"Phang","year":"2021","journal-title":"Amino Acids"},{"key":"ref_57","first-page":"28","article-title":"Interconnections within the Tumor Microenvironment: Extracellular Vesicles as Critical Players of Metabolic Reprogramming in Tumor Cells","volume":"10","author":"Faria","year":"2024","journal-title":"J. Cancer Metastasis Treat."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/7\/1074\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T15:47:08Z","timestamp":1775058428000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/7\/1074"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,25]]},"references-count":57,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["molecules31071074"],"URL":"https:\/\/doi.org\/10.3390\/molecules31071074","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,25]]}}}