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.

Abstract

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.

• Authors: Ji-Na Pak, Ji Hoon Jung, Ji Eon Park, Jisung Hwang, Hyo Jung Lee, Bum-Sang Shim, Sung-Hoon Kim
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 34 Issue 10 Pg. 2745-2755 (Oct 2020) ISSN: 1099-1573 [Electronic] England
• PMID: 32403193 (Publication Type: Journal Article)
• Copyright: © 2020 John Wiley & Sons, Ltd.

Chemical References

• Ginsenosides
• LGR5 protein, human
• Receptors, G-Protein-Coupled
• Tumor Suppressor Protein p53
• ginsenoside M1
• CASP3 protein, human
• Caspase 3

Topics

• Apoptosis
• Caspase 3 (metabolism)
• Cell Line, Tumor
• Colorectal Neoplasms (genetics, pathology)
• Ginsenosides (pharmacology, therapeutic use)
• HCT116 Cells (metabolism)
• Humans
• Receptors, G-Protein-Coupled (antagonists & inhibitors)
• Tumor Suppressor Protein p53 (metabolism)