Naturally occurring aesculetin coumarin exerts antiproliferative effects in gastric cancer cells mediated via apoptotic cell death, cell cycle arrest and targeting PI3K/AKT/M-TOR signalling pathway

Abstract

Aesculetin is an active member of coumarins that has been reported to possess significant medicinal and biological importance. It has also been shown with potential anticancer activity against different human cancers including breast, lung and hepatocellular carcinoma. Therefore, the current investigation was undertaken to examine the anticancer effects of aesculetin against gastric cancer. MTT assay was performed to check the cellular viability and clonogenic assay was executed to assess the effect of aesculetin on colony formation capacity of SGC-7901 gastric cancer cells. Apoptosis was analysed by AO/EB staining and annexin V-FITC/PI staining assays. Cell cycle phases were monitored using flowcytometry and western blotting was used to detect the effects of aesculetin on PI3K/AKT/M-TOR signalling pathway. Results indicated that aesculetin not only reduced the cellular proliferation in time-dependent manner but dose-dependent manner as well. Clonogenic tendency of SGC-7901 cells was retarded significantly by the aesculetin. The antiproliferative effects of aesculetin may arbitrate via apoptosis. Further, flow cytometric analysis revealed that the G2/M-phase SGC-7901 cells amplified number with increasing aesculetin doses. Indicating blocking of cell cycle at G2/M-phase. Finally, western blotting assay suggested blocking of PI3K/AKT/M-TOR signalling pathway by aesculetin in gastric cancer SGC-7901 cells. Taking altogether, aesculetin could induce significant growth inhibitory effects against gastric cancer SGC-7901 cells. Moreover, aesculetin could induce apoptotic cell death, cell cycle arrest and block PI3K/AKT/M-TOR signalling pathway.