BMC pharmacology & toxicology · 2025
Repurposing DPP-4 inhibitors as anticancer agents in KRAS-mutated pancreatic ductal adenocarcinoma.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Ramalingam Prasanna Srinivasan, Hussain Md Sadique, Chellasamy Gayathri, Elangovan Sujatha, Sharma Divya, T Premkumar, Mishra Rudra Awdhesh Kumar, Kodiveri Muthukaliannan Gothandam, Hussain Tajamul, Alrokayan Salman, Balakrishnan Purushothaman, Mekala Janaki Ramaiah, Arumugam Sivakumar
Аннотация
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.