{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["26(1)"],"submitter":["Ramalingam PS"],"pubmed_abstract":["<h4>Background</h4>Cancer has become a global health threat with increasing incidence & mortality rates, and despite significant advancements in diagnostics and therapeutics, they limited for aggressive cancers like pancreatic ductal adenocarcinoma (PDAC). To note, KRAS-mutated PDAC is very frequent and limited by potent therapeutics due to their aggressiveness. Drug repurposing has become a potent strategy due to cost-effective, established safety & toxicity profiles. Sitagliptin and Linagliptin are Dipeptidyl Peptidase-4 (DPP-4) inhibitors, which are being used to manage Type 2 Diabetes Mellitus (T2DM). Recent studies have indicated that they have the potential to induce apoptotic-mediated cell death in cancer.<h4>Methods</h4>In the current study, we examined the therapeutic potential of these DPP-4 inhibitors in proliferation, wound healing, and colony formation, ROS induction, DNA fragmentation, apoptosis induction, and regulation of gene expression in KRAS G12C-mutated MIA PaCa-2 & KRAS G12D-mutated PANC-1 PDAC cells. Additionally, the network pharmacology, Gene Ontology (GO) & KEGG pathways enrichment were also studied for DPP-4 inhibitors in PDAC.<h4>Results</h4>The results indicated that both drugs inhibited the proliferation, migration, & colony formation; elevated intracellular ROS levels; induced DNA fragmentation, regulated MAPK & apoptosis-related gene expression, and induced apoptosis confirmed by flow cytometry. In addition, the network pharmacology analysis supported that the identified hub genes plays a role in apoptosis.<h4>Conclusions</h4>Overall, we report that Sitagliptin and Linagliptin have significant anticancer potential towards KRAS-mutated PDAC. Furthermore, we recommend repurposing of more drugs to examine their anti-cancer potential towards these aggressive cancers and to overcome clinical resistance in the near future."],"journal":["BMC pharmacology & toxicology"],"pagination":["208"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12687489"],"repository":["biostudies-literature"],"pubmed_title":["Repurposing DPP-4 inhibitors as anticancer agents in KRAS-mutated pancreatic ductal adenocarcinoma."],"pmcid":["PMC12687489"],"pubmed_authors":["Chellasamy G","T P","Kodiveri Muthukaliannan G","Arumugam S","Mekala JR","Hussain MS","Ramalingam PS","Sharma D","Hussain T","Mishra RAK","Alrokayan S","Balakrishnan P","Elangovan S"],"additional_accession":[]},"is_claimable":false,"name":"Repurposing DPP-4 inhibitors as anticancer agents in KRAS-mutated pancreatic ductal adenocarcinoma.","description":"<h4>Background</h4>Cancer has become a global health threat with increasing incidence & mortality rates, and despite significant advancements in diagnostics and therapeutics, they limited for aggressive cancers like pancreatic ductal adenocarcinoma (PDAC). To note, KRAS-mutated PDAC is very frequent and limited by potent therapeutics due to their aggressiveness. Drug repurposing has become a potent strategy due to cost-effective, established safety & toxicity profiles. Sitagliptin and Linagliptin are Dipeptidyl Peptidase-4 (DPP-4) inhibitors, which are being used to manage Type 2 Diabetes Mellitus (T2DM). Recent studies have indicated that they have the potential to induce apoptotic-mediated cell death in cancer.<h4>Methods</h4>In the current study, we examined the therapeutic potential of these DPP-4 inhibitors in proliferation, wound healing, and colony formation, ROS induction, DNA fragmentation, apoptosis induction, and regulation of gene expression in KRAS G12C-mutated MIA PaCa-2 & KRAS G12D-mutated PANC-1 PDAC cells. Additionally, the network pharmacology, Gene Ontology (GO) & KEGG pathways enrichment were also studied for DPP-4 inhibitors in PDAC.<h4>Results</h4>The results indicated that both drugs inhibited the proliferation, migration, & colony formation; elevated intracellular ROS levels; induced DNA fragmentation, regulated MAPK & apoptosis-related gene expression, and induced apoptosis confirmed by flow cytometry. In addition, the network pharmacology analysis supported that the identified hub genes plays a role in apoptosis.<h4>Conclusions</h4>Overall, we report that Sitagliptin and Linagliptin have significant anticancer potential towards KRAS-mutated PDAC. Furthermore, we recommend repurposing of more drugs to examine their anti-cancer potential towards these aggressive cancers and to overcome clinical resistance in the near future.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-05-23T03:23:16.536Z","creation":"2026-05-23T03:13:55.508Z"},"accession":"S-EPMC12687489","cross_references":{"pubmed":["41361888"],"doi":["10.1186/s40360-025-01020-z"]}}