{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T05:04:59Z","timestamp":1780549499743,"version":"3.54.1"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Phenformin, a representative of the biguanides class was previously used for treatment of type 2 diabetes and discontinued due to a risk of causing lactic acidosis, has shown promising anticancer activity in numerous studies. Since many types of cancer arise and proliferate due to dysregulation in apoptotic or autophagic pathways, this study aimed to assess the underlying anticancer effects of phenformin in terms of these two processes. We initially set out to examine the antiproliferative effects of phenformin on multiple cancer cell lines including breast, pancreatic, cervical cancers, hepatocellular carcinoma and malignant melanoma. Subsequently, the expression of apoptosis and autophagy related proteins was measured in the cervical cancer cell lines found to be the most susceptible to antiproliferative effects of phenformin. Additionally, the ability of phenformin to potentiate the antitumor effect of resveratrol and vistusertib was assessed. Phenformin increased the expression of pro-apoptotic factor, Bax, and lowered the level of anti-apoptotic protein, Bcl-2. Hence, it was proposed that phenformin promotes antiproliferative activity by inducing apoptosis. Our findings demonstrate that phenformin decreases the proliferation of various cancer cell lines in a dose-dependent manner and may have an ability to increase the autophagic flux in cervical cancer cells. Our findings demonstrate that phenformin decreases the proliferation of various cancer cell lines in a dose-dependent manner potentially by inducing apoptosis.<\/jats:p>","DOI":"10.3390\/ijms27114941","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"4941","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phenformin-Induced Apoptosis: A Potential Mechanism for Cervical Cancer Cell Inhibition"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9212-7786","authenticated-orcid":false,"given":"Gehad M.","family":"Subaiea","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, University of Ha\u2019il, Hail 55473, Saudi Arabia"},{"name":"Medical and Diagnostic Research Center, University of Ha\u2019il, Hail 55473, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yernar","family":"Amangelsin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine, Nazarbayaev University, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"Sagatbekova","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine, Nazarbayaev University, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2235-8957","authenticated-orcid":false,"given":"Ahmed A.","family":"Katamesh","sequence":"additional","affiliation":[{"name":"Medical and Diagnostic Research Center, University of Ha\u2019il, Hail 55473, Saudi Arabia"},{"name":"Department of Pharmaceutics, College of Pharmacy, University of Ha\u2019il, Hail 55473, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8538-5250","authenticated-orcid":false,"given":"Sameer A.","family":"Alkubati","sequence":"additional","affiliation":[{"name":"Medical and Diagnostic Research Center, University of Ha\u2019il, Hail 55473, Saudi Arabia"},{"name":"Department of Medical Surgical Nursing, College of Nursing, University of Ha\u2019il, Hail 55473, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"Alobaida","sequence":"additional","affiliation":[{"name":"Medical and Diagnostic Research Center, University of Ha\u2019il, Hail 55473, Saudi Arabia"},{"name":"Department of Pharmaceutics, College of Pharmacy, University of Ha\u2019il, Hail 55473, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan Abdelmawgoud","family":"Atia","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, University of Ha\u2019il, Hail 55473, Saudi Arabia"},{"name":"Medical and Diagnostic Research Center, University of Ha\u2019il, Hail 55473, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9300-3515","authenticated-orcid":false,"given":"Nasrin E.","family":"Khalifa","sequence":"additional","affiliation":[{"name":"Medical and Diagnostic Research Center, University of Ha\u2019il, Hail 55473, Saudi Arabia"},{"name":"Department of Pharmaceutics, College of Pharmacy, University of Ha\u2019il, Hail 55473, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5630-2468","authenticated-orcid":false,"given":"Thamir M.","family":"Alshammari","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7518-7365","authenticated-orcid":false,"given":"Reezal","family":"Ishak","sequence":"additional","affiliation":[{"name":"Institute of Medical Science Technology (UniKL MESTECH), Universiti Kuala Lumpur, A1-1, Jalan TKS 1, Taman Kajang Sentral, Kajang 43000, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Aljofan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Medicine, Nazarbayaev University, Astana 010000, Kazakhstan"},{"name":"Institute of Medical Science Technology (UniKL MESTECH), Universiti Kuala Lumpur, A1-1, Jalan TKS 1, Taman Kajang Sentral, Kajang 43000, Selangor, Malaysia"},{"name":"National Laboratory Astana, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","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. 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