p53 dependent LGR5 inhibition and caspase 3 activation are critically involved in apoptotic effect of compound K and its combination therapy potential in HCT116 cells

Though ginsenoside metabolite compound K was known to have antitumor effect in several cancers, its underlying apoptotic mechanism still remains unclear so far. Thus, in the present study, the apoptotic mechanism of compound K was explored in colorectal cancer cells (CRCs) in association with leucine rich repeat containing G protein‐coupled receptor 5 (LGR5) that was overexpressed in colorectal cancers with poor survival rate. Here compound K significantly reduced viability of HCT116p53+/+ cells better than that of HCT116p53−/−cells. Consistently, compound K increased sub G1 population and attenuated the expression of LGR5, c‐Myc, procaspase3, Pin1 in HCT116p53+/+ cells more than in HCT116p53−/− cells. Conversely, caspase 3 inhibitor Z‐DEVD‐FMK reversed inhibitory effect of compound K on LGR5, c‐Myc and procaspase3 in HCT116 cells. Consistently, inhibition of LGR5 using transfection method enhanced suppression of pro‐PARP, Bcl‐xL c‐Myc, Snail and Pin1 in compound K treated HCT116p53+/+ cells. Furthermore, compound K synergistically potentiated antitumor effect of 5‐fluorouracil (5‐FU) or Doxorubicin to reduce the survival genes and cytotoxicity in HCT116p53+/+ cells. Overall, our findings provide scientific insight that compound K induces apoptosis in colon cancer cells via caspase and p53 dependent LGR5 inhibition with combination therapy potential with 5‐FU or doxorubicin.