首页|Isoprenylated Coumarin Exhibits Anti-proliferative Effects in Pancreatic Cancer Cells Under Nutrient Starvation by Inhibiting Autophagy
Isoprenylated Coumarin Exhibits Anti-proliferative Effects in Pancreatic Cancer Cells Under Nutrient Starvation by Inhibiting Autophagy
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NSTL
Int Inst Anticancer Research
Background/Aim: Due to the lack of early detection methods and effective treatments, pancreatic cancer has one of the lowest five-year survival rates among all cancers. We have previously identified novel isoprenylated coumarin compounds that exhibit preferential cytotoxicity against pancreatic adenocarcinoma cell line PANC-1 exclusively under glucose deprivation conditions. Materials and Methods: Using cell cytotoxicity assays, we investigated the anti-proliferative mechanism of our most potent isoprenylated coumarin compound of the series, DCM-MJ-I-21, with respect to time, against two other pancreatic cancer cell lines, BxPC-3 and Capan-2. We used western blotting to quantify the autophagic flux influenced by our compound, autophagy inducers (starvation and Rapamycin), and autophagy inhibitors (chloroquine and wortmannin). Results: We observed a clear dependence on glucose in DCM-MJ-I-21 in BxPC-3 and Capan-2 pancreatic cancer cell lines, suggesting that our compound targets a pathway shared by these cancer cell lines when glycolysis is not an option for survival. Our lead compound increased the conversion of LC3-I to LC3-II in PANC-1, similar to the effect of chloroquine, an autophagy inhibitor. In addition, Spautin-1, another autophagy inhibitor, showed almost the same anti-proliferative activities at the same concentration under nutrient-deprived conditions as our lead compound in both 2D and 3D cell cultures. Conclusion: Our lead isoprenylated coumarin compound induces selective pancreatic cancer cell death under nutrient-deprived conditions through inhibition of autophagy, potentially providing insights into new therapeutic options.
Novel anti-pancreatic cancer agentcoumarin derivativeselective cytotoxicityautophagyLC3ADENOCARCINOMADEPRIVATIONTOLERANCE
Zhou, Ronghao、Kusaka, Erika、Wang, Yin、Zhang, Jing、Webb, Andrew、Carrico-Moniz, Dora
NSTL
Int Inst Anticancer Research
