Anticancer Effect and Molecular Docking Mechanism of 24-OH-panaxadiol / 中国实验方剂学杂志

ABSTRACT

Objective:To investigate the effect of ginsenoside 20(S),25-epoxydammarane-3β,12β,24α-triol (24-OH-panaxadiol,24-OH-PD) on inhibiting proliferation and inducing apoptosis of tumor cells, and explore its mechanism of action. Method:The inhibitory effect of 24-OH-PD (12.5,25,50,100 mg·L-1) on proliferation of CCRF-CEM, M14, MD-MBA-231 and Jeko-1 cells with different treatment periods (24, 48,72 h) was evaluated by methylthiazolyldiphenyl-tetrazolium bromide (MTT)assay and CellTiter Glo test, and the results were then compared with 20(R)-Rg3 and 20(S)-Rh2.Flow cytometry was used to detect cell apoptosis caused by 24-OH-PD. Besides, the potential anticancer mechanism was studied by docking analysis with 40 cancer related proteins and 24-OH-PD by using drug design platform Schrodinger Maestro 6.7 Software. Result:24-OH-PD inhibited the proliferation of all the 4 cancer cell lines significantly in a time and dosage dependent manner. The IC50 value of 24-OH-PD on CCRF-CEM,Jeko-1,M14,and MD-MBA-231 cell lines was 25.36, 39.29, 21.74, and 19.35 mg·L-1, respectively, similar to 20(S)-Rh2 (IC50 23.35, 65.79, 18.95, 19.67 mg·L-1) and much better than 20(R)-Rg3 (only effective for Jeko-1 cells, IC50 49.5 mg·L-1). Annexin V/PI double staining experiment showed that 24-OH-PD could also induce apoptosis of the 4 kinds of cancer cells (PConclusion:24-OH-PD could inhibit cell proliferation and induce apoptosis for CCRF-CEM, M14, MD-MBA-231 and Jeko-1 cell lines, which may through directly acting on Bcl-2, Bcl-xl, and other proteins.