{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:13:21Z","timestamp":1790050401860,"version":"4.0.1"},"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021772","name":"Deanship of Scientific Research, University of Jordan","doi-asserted-by":"publisher","award":["2566"],"award-info":[{"award-number":["2566"]}],"id":[{"id":"10.13039\/501100021772","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Deanship of Scientific Research, AlZaytoonah University of Jordan","award":["2023-2022\/17\/50"],"award-info":[{"award-number":["2023-2022\/17\/50"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide and the second leading cause of cancer-related deaths. Despite advances in treatment, drug resistance remains a critical challenge. Dipeptidyl peptidase 4 (DPP4), a multifunctional cell surface protein, shows variable expression across malignancies and plays a role in cancer biology. DPP4 inhibitors, initially developed as antidiabetic agents, have demonstrated anticancer properties in several cancer types. In this study, network pharmacology analysis revealed that DPP4 inhibitors modulate critical cancer-associated pathways, such as proteoglycans in cancer, ECM(extracellular matrix)-receptor interaction, and PI3K-AKT (phosphatidylinositol 3-kinase\u2013protein kinase B) signaling. Experimental data showed dose-dependent growth inhibition in four CRC cell lines treated with FDA (Food and Drug Administration)-approved and novel DPP4 inhibitors. Combination treatments with doxorubicin yielded synergistic effects, whereas those with 5-fluorouracil (5FU) were either synergistic or additive. The examined DPP4 inhibitors effectively suppressed colony formation in HCT-116 cells and induced apoptosis. Additionally, the inhibitors resulted in G0\/G1 cell cycle arrest and significantly reduced the expression of <jats:italic>CD26 (Cluster of Differentiation 26)<\/jats:italic>, <jats:italic>Bcl-2(B-cell lymphoma 2)<\/jats:italic>, and <jats:italic>VEGF (Vascular Endothelial Growth Factor)<\/jats:italic> in HCT-116 cells. Our findings highlight the potential therapeutic utility of DPP4 inhibitors in CRC treatment, either as standalone agents or in combination with standard chemotherapeutics. Moreover, the computational insights provided herein enhance our understanding of the molecular mechanisms underlying the anticancer effects of DPP4 inhibitors, paving the way for their potential clinical application.<\/jats:p>","DOI":"10.1371\/journal.pone.0334223","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:35:48Z","timestamp":1760117748000},"page":"e0334223","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["DPP4 inhibitors as a novel therapeutic strategy in colorectal cancer: Integrating network biology and experimental insights"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4823-0708","authenticated-orcid":true,"given":"Sanaa K.","family":"Bardaweel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baraa","family":"Abu Sneineh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima","family":"Hajjo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reema","family":"Abu Khalaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"pone.0334223.ref001","article-title":"Cancer treatment and chemotherapy.","volume-title":"Pharmacotherapy: a pathophysiologic approach","author":"LM Cordes","year":"2020","edition":"11"},{"issue":"3","key":"pone.0334223.ref002","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":"H Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"pone.0334223.ref003","first-page":"7","article-title":"Cancer statistics, 2022.","volume":"72","author":"RL Siegel","year":"2022","journal-title":"CA"},{"key":"pone.0334223.ref004","article-title":"Colorectal adenocarcinoma: risks, prevention and diagnosis","volume":"354","author":"SG Thrumurthy","year":"2016","journal-title":"BMJ"},{"issue":"9","key":"pone.0334223.ref005","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.5306\/wjco.v15.i9.1136","article-title":"Colorectal cancer: recent advances in management and treatment","volume":"15","author":"H Fadlallah","year":"2024","journal-title":"World J Clin Oncol"},{"issue":"4","key":"pone.0334223.ref006","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1051\/bmdcn\/2017070423","article-title":"A review on the effects of current chemotherapy drugs and natural agents in treating non-small cell lung cancer","volume":"7","author":"C-Y Huang","year":"2017","journal-title":"Biomedicine (Taipei)"},{"issue":"30","key":"pone.0334223.ref007","doi-asserted-by":"crossref","first-page":"10316","DOI":"10.3748\/wjg.v20.i30.10316","article-title":"FOLFOX\/FOLFIRI pharmacogenetics: the call for a personalized approach in colorectal cancer therapy","volume":"20","author":"B Mohelnikova-Duchonova","year":"2014","journal-title":"World J Gastroenterol"},{"issue":"2","key":"pone.0334223.ref008","doi-asserted-by":"crossref","first-page":"179","DOI":"10.2478\/acph-2020-0020","article-title":"Proton pump inhibitors enhance chemosensitivity, promote apoptosis, and suppress migration of breast cancer cells","volume":"70","author":"WG Ihraiz","year":"2020","journal-title":"Acta Pharm"},{"issue":"34","key":"pone.0334223.ref009","doi-asserted-by":"crossref","first-page":"3834","DOI":"10.3748\/wjg.v24.i34.3834","article-title":"Drug resistance and new therapies in colorectal cancer","volume":"24","author":"K Van der Jeught","year":"2018","journal-title":"World J Gastroenterol"},{"issue":"10","key":"pone.0334223.ref010","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.1007\/s11010-021-04191-5","article-title":"Doxorubicin-paclitaxel sequential treatment: insights of DNA methylation and gene expression changes of luminal A and triple negative breast cancer cell lines","volume":"476","author":"L Hamadneh","year":"2021","journal-title":"Mol Cell Biochem"},{"issue":"6","key":"pone.0334223.ref011","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.ceb.2006.10.005","article-title":"Glucose metabolism and cancer","volume":"18","author":"RJ Shaw","year":"2006","journal-title":"Curr Opin Cell Biol"},{"issue":"4","key":"pone.0334223.ref012","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1677\/ERC-09-0087","article-title":"Diabetes and cancer","volume":"16","author":"P Vigneri","year":"2009","journal-title":"Endocr Relat Cancer"},{"issue":"3","key":"pone.0334223.ref013","doi-asserted-by":"crossref","first-page":"495","DOI":"10.2337\/dc14-1175","article-title":"The risk of colorectal cancer in patients with type 2 diabetes: associations with treatment stage and obesity","volume":"38","author":"PJHL Peeters","year":"2015","journal-title":"Diabetes Care"},{"issue":"7","key":"pone.0334223.ref014","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.2337\/dc10-0666","article-title":"Diabetes and cancer: a consensus report","volume":"33","author":"E Giovannucci","year":"2010","journal-title":"Diabetes Care"},{"issue":"8","key":"pone.0334223.ref015","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/S0969-2126(03)00160-6","article-title":"Structural basis of proline-specific exopeptidase activity as observed in human dipeptidyl peptidase-IV","volume":"11","author":"R Thoma","year":"2003","journal-title":"Structure"},{"issue":"2","key":"pone.0334223.ref016","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1110\/ps.03460604","article-title":"Crystal structure of human dipeptidyl peptidase IV in complex with a decapeptide reveals details on substrate specificity and tetrahedral intermediate formation","volume":"13","author":"K Aertgeerts","year":"2004","journal-title":"Protein Sci"},{"issue":"10","key":"pone.0334223.ref017","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s12032-023-02140-4","article-title":"Metformin as a promising target for DPP4 expression: computational modeling and experimental validation","volume":"40","author":"AA El-Arabey","year":"2023","journal-title":"Med Oncol"},{"key":"pone.0334223.ref018","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.pharmthera.2019.02.015","article-title":"CD26\/DPP4 - a potential biomarker and target for cancer therapy","volume":"198","author":"N Enz","year":"2019","journal-title":"Pharmacol Ther"},{"issue":"9","key":"pone.0334223.ref019","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.3390\/cancers13092191","article-title":"CD26\/DPP-4: Type 2 diabetes drug target with potential influence on cancer biology","volume":"13","author":"E Kawakita","year":"2021","journal-title":"Cancers (Basel)"},{"key":"pone.0334223.ref020","doi-asserted-by":"crossref","first-page":"4347936","DOI":"10.1155\/2020\/4347936","article-title":"CD26-related serum biomarkers: sCD26 protein, DPP4 activity, and Anti-CD26 isotype levels in a colorectal cancer-screening context","volume":"2020","author":"L De Chiara","year":"2020","journal-title":"Dis Markers"},{"issue":"3","key":"pone.0334223.ref021","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0119436","article-title":"Dipeptidyl-peptidase IV activity is correlated with colorectal cancer prognosis","volume":"10","author":"G Larrinaga","year":"2015","journal-title":"PLoS One"},{"issue":"15","key":"pone.0334223.ref022","doi-asserted-by":"crossref","first-page":"2720","DOI":"10.3390\/ijerph16152720","article-title":"The role of DPP-4 inhibitors in the treatment algorithm of type 2 diabetes mellitus: when to select, what to expect","volume":"16","author":"K Makrilakis","year":"2019","journal-title":"Int J Environ Res Public Health"},{"issue":"7","key":"pone.0334223.ref023","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s10585-015-9736-z","article-title":"Suppression of lung metastases by the CD26\/DPP4 inhibitor Vildagliptin in mice","volume":"32","author":"J-H Jang","year":"2015","journal-title":"Clin Exp Metastasis"},{"issue":"2","key":"pone.0334223.ref024","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1093\/carcin\/bgz009","article-title":"The CD26\/DPP4-inhibitor vildagliptin suppresses lung cancer growth via macrophage-mediated NK cell activity","volume":"40","author":"J-H Jang","year":"2019","journal-title":"Carcinogenesis"},{"key":"pone.0334223.ref025","article-title":"Repositioning of hypoglycemic drug linagliptin for cancer treatment","volume":"11","author":"Y Li","year":"2020","journal-title":"Front Pharmacol"},{"issue":"33","key":"pone.0334223.ref026","doi-asserted-by":"crossref","first-page":"35703","DOI":"10.1021\/acsomega.4c04100","article-title":"Unveiling the Intricacies of Monoamine Oxidase-A (MAO-A) inhibition in colorectal cancer: computational systems biology, expression patterns, and the anticancer therapeutic potential","volume":"9","author":"SK Bardaweel","year":"2024","journal-title":"ACS Omega"},{"issue":"46","key":"pone.0334223.ref027","doi-asserted-by":"crossref","first-page":"29765","DOI":"10.1021\/acsomega.0c03597","article-title":"Chemocentric informatics analysis: dexamethasone versus combination therapy for COVID-19","volume":"5","author":"R Hajjo","year":"2020","journal-title":"ACS Omega"},{"issue":"7","key":"pone.0334223.ref028","doi-asserted-by":"crossref","DOI":"10.3390\/pathogens11070743","article-title":"Analyzing the systems biology effects of COVID-19 mRNA vaccines to assess their safety and putative side effects","volume":"11","author":"R Hajjo","year":"2022","journal-title":"Pathogens"},{"issue":"11","key":"pone.0334223.ref029","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"P Shannon","year":"2003","journal-title":"Genome Res"},{"key":"pone.0334223.ref030","article-title":"STRING v9.1: protein-protein interaction networks, with increased coverage and integration","volume":"41","author":"A Franceschini","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"pone.0334223.ref031","doi-asserted-by":"crossref","first-page":"2592691","DOI":"10.1155\/2023\/2592691","article-title":"Molecular investigation of the antitumor effects of monoamine oxidase inhibitors in breast cancer cells","volume":"2023","author":"A Alkhawaldeh","year":"2023","journal-title":"Biomed Res Int"},{"issue":"9","key":"pone.0334223.ref032","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.2174\/1871520621666210908110902","article-title":"Selective Estrogen Receptor Modulators (SERMs) synergize with cisplatin, induce apoptosis and suppress cellular migration and colony formation of lung cancer cells","volume":"22","author":"L Alsous","year":"2022","journal-title":"Anticancer Agents Med Chem"},{"issue":"2","key":"pone.0334223.ref033","doi-asserted-by":"crossref","first-page":"142","DOI":"10.2174\/1573409914666180308164013","article-title":"Synthesis, structural characterization and docking studies of sulfamoyl- phenyl acid esters as dipeptidyl peptidase-IV inhibitors","volume":"14","author":"RA Khalaf","year":"2018","journal-title":"Curr Comput Aided Drug Des"},{"key":"pone.0334223.ref034","doi-asserted-by":"crossref","first-page":"39","DOI":"10.2174\/1874104501307010039","article-title":"Design, synthesis and biological evaluation of N4-sulfonamido-succinamic, phthalamic, acrylic and benzoyl acetic acid derivatives as potential DPP IV inhibitors","volume":"7","author":"RA Khalaf","year":"2013","journal-title":"Open Med Chem J"},{"key":"pone.0334223.ref035","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1186\/1472-6882-14-297","article-title":"Antioxidant, antimicrobial and antiproliferative activities of Anthemis palestina essential oil","volume":"14","author":"SK Bardaweel","year":"2014","journal-title":"BMC Complement Altern Med"},{"issue":"15","key":"pone.0334223.ref036","doi-asserted-by":"crossref","first-page":"15204","DOI":"10.1021\/acsomega.4c10939","article-title":"Unraveling the anticancer potential of SSRIs in prostate cancer by combining computational systems biology and in vitro analyses","volume":"10","author":"SK Bardaweel","year":"2025","journal-title":"ACS Omega"},{"key":"pone.0334223.ref037","doi-asserted-by":"crossref","first-page":"108131","DOI":"10.1016\/j.bioorg.2025.108131","article-title":"Discovery of novel tris-1,2,3-triazole-based hybrids as VEGFR2 inhibitors with potent anti-proliferative and cytotoxicity through apoptosis induction","volume":"155","author":"M Alsehli","year":"2025","journal-title":"Bioorg Chem"},{"issue":"10","key":"pone.0334223.ref038","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/ng.2764","article-title":"The cancer genome atlas pan-cancer analysis project","volume":"45","author":"Cancer Genome Atlas Research Network","year":"2013","journal-title":"Nat Genet"},{"issue":"269","key":"pone.0334223.ref039","article-title":"Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal","volume":"6","author":"J Gao","year":"2013","journal-title":"Sci Signal"},{"issue":"5","key":"pone.0334223.ref040","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1002\/iub.2454","article-title":"The mechanism of sitagliptin inhibition of colorectal cancer cell lines\u2019 metastatic functionalities","volume":"73","author":"R Varela-Calvi\u00f1o","year":"2021","journal-title":"IUBMB Life"},{"issue":"12","key":"pone.0334223.ref041","article-title":"Evaluation of anti cancer effects of DPP-4 inhibitors in colon cancer- an invitro study","volume":"9","author":"CA Amritha","year":"2015","journal-title":"J Clin Diagn Res"},{"issue":"11","key":"pone.0334223.ref042","doi-asserted-by":"crossref","first-page":"3816","DOI":"10.1002\/cam4.3024","article-title":"Sitagliptin affects gastric cancer cells proliferation by suppressing Melanoma-associated antigen-A3 expression through Yes-associated protein inactivation","volume":"9","author":"Q Wang","year":"2020","journal-title":"Cancer Med"},{"issue":"10","key":"pone.0334223.ref043","first-page":"1010428317722068","article-title":"The dipeptidyl peptidase-IV inhibitor gemigliptin alone or in combination with NVP-AUY922 has a cytotoxic activity in thyroid carcinoma cells","volume":"39","author":"SH Kim","year":"2017","journal-title":"Tumour Biol"},{"issue":"21","key":"pone.0334223.ref044","doi-asserted-by":"crossref","first-page":"5096","DOI":"10.1111\/bph.13274","article-title":"Dipeptidyl peptidase 4 promotes epithelial cell transformation and breast tumourigenesis via induction of PIN1 gene expression","volume":"172","author":"HJ Choi","year":"2015","journal-title":"Br J Pharmacol"},{"issue":"5","key":"pone.0334223.ref045","doi-asserted-by":"crossref","first-page":"8679","DOI":"10.18632\/oncotarget.14412","article-title":"DPPIV promotes endometrial carcinoma cell proliferation, invasion and tumorigenesis","volume":"8","author":"X Yang","year":"2017","journal-title":"Oncotarget"},{"issue":"33","key":"pone.0334223.ref046","doi-asserted-by":"crossref","first-page":"11727","DOI":"10.3748\/wjg.v20.i33.11727","article-title":"MicroRNAs as novel predictive biomarkers and therapeutic targets in colorectal cancer","volume":"20","author":"V Stiegelbauer","year":"2014","journal-title":"World J Gastroenterol"},{"key":"pone.0334223.ref047","doi-asserted-by":"crossref","first-page":"111285","DOI":"10.1016\/j.biopha.2021.111285","article-title":"5-Fluorouracil (5-FU) resistance and the new strategy to enhance the sensitivity against cancer: Implication of DNA repair inhibition","volume":"137","author":"C Sethy","year":"2021","journal-title":"Biomed Pharmacother"},{"issue":"22","key":"pone.0334223.ref048","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1093\/jnci\/djp328","article-title":"Pharmacokinetically guided dose adjustment of 5-fluorouracil: a rational approach to improving therapeutic outcomes","volume":"101","author":"MW Saif","year":"2009","journal-title":"J Natl Cancer Inst"},{"key":"pone.0334223.ref049","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.canlet.2020.10.009","article-title":"Angiogenesis is promoted by exosomal DPP4 derived from 5-fluorouracil-resistant colon cancer cells","volume":"497","author":"X Zheng","year":"2021","journal-title":"Cancer Lett"},{"issue":"7","key":"pone.0334223.ref050","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1097\/FPC.0b013e32833ffb56","article-title":"Doxorubicin pathways: pharmacodynamics and adverse effects","volume":"21","author":"CF Thorn","year":"2011","journal-title":"Pharmacogenet Genomics"},{"issue":"14","key":"pone.0334223.ref051","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1177\/1535370216643418","article-title":"Cardioprotective effects of sitagliptin against doxorubicin-induced cardiotoxicity in rats","volume":"241","author":"DS El-Agamy","year":"2016","journal-title":"Exp Biol Med (Maywood)"},{"issue":"3","key":"pone.0334223.ref052","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1159\/000490688","article-title":"Anti-inflammatory action of sitagliptin and linagliptin in doxorubicin nephropathy","volume":"43","author":"CH Jo","year":"2018","journal-title":"Kidney Blood Press Res"},{"key":"pone.0334223.ref053","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.cca.2007.02.037","article-title":"Serum macrophage-colony stimulating factor levels in colorectal cancer patients correlate with lymph node metastasis and poor prognosis","volume":"380","author":"B Mroczko","year":"2007","journal-title":"Clin Chim Acta"},{"issue":"21","key":"pone.0334223.ref054","doi-asserted-by":"crossref","first-page":"5096","DOI":"10.1111\/bph.13274","article-title":"Dipeptidyl peptidase 4 promotes epithelial cell transformation and breast tumourigenesis via induction of PIN1 gene expression","volume":"172","author":"HJ Choi","year":"2015","journal-title":"Br J Pharmacol"},{"issue":"5","key":"pone.0334223.ref055","article-title":"Prognostic significance of CD26 in patients with colorectal cancer","volume":"9","author":"CSC Lam","year":"2014","journal-title":"PLoS One"},{"key":"pone.0334223.ref056","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ejps.2016.12.040","article-title":"Sitagliptin inhibit human lymphocytes proliferation and Th1\/Th17 differentiation in vitro","volume":"100","author":"MM Pinheiro","year":"2017","journal-title":"Eur J Pharm Sci"},{"issue":"6","key":"pone.0334223.ref057","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1007\/s00384-003-0576-y","article-title":"Vascular endothelial growth factor in colorectal cancer","volume":"19","author":"M Guba","year":"2004","journal-title":"Int J Colorectal Dis"},{"key":"pone.0334223.ref058","doi-asserted-by":"crossref","first-page":"720173","DOI":"10.3389\/fphar.2021.720173","article-title":"AKT-AMPK\u03b1-mTOR-dependent HIF-1\u03b1 activation is a new therapeutic target for cancer treatment: a novel approach to repositioning the antidiabetic drug sitagliptin for the management of hepatocellular carcinoma","volume":"12","author":"EE Abd El-Fattah","year":"2022","journal-title":"Front Pharmacol"},{"issue":"3","key":"pone.0334223.ref059","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a026104","article-title":"The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression","volume":"6","author":"J Chen","year":"2016","journal-title":"Cold Spring Harb Perspect Med"},{"issue":"1","key":"pone.0334223.ref060","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nrm3722","article-title":"Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy","volume":"15","author":"PE Czabotar","year":"2014","journal-title":"Nat Rev Mol Cell Biol"},{"key":"pone.0334223.ref061","doi-asserted-by":"crossref","first-page":"11","DOI":"10.22270\/jddt.v7i6.1519","article-title":"Antiproliferative and apoptogenic efficacy of antidiabetic drugs metformin and sitagliptin against MCF7 and HepG2 cancer cells: a comparative molecular study","volume":"7","author":"M Sarkar","year":"2017","journal-title":"J Drug Delivery Therapeutics"},{"issue":"10","key":"pone.0334223.ref062","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/S0968-0004(00)89093-3","article-title":"Cellular responses to DNA damage: cell-cycle checkpoints, apoptosis and the roles of p53 and ATM","volume":"20","author":"T Enoch","year":"1995","journal-title":"Trends Biochem Sci"},{"issue":"4","key":"pone.0334223.ref063","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/sj.neo.7900101","article-title":"Cell cycle and apoptosis","volume":"2","author":"B Pucci","year":"2000","journal-title":"Neoplasia"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0334223","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:35:57Z","timestamp":1760117757000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0334223"}},"subtitle":[],"editor":[{"given":"Amr Ahmed","family":"El-Arabey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,10]]},"references-count":63,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0334223","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,10]]}}}