Anticancer Effect and Molecular Docking Mechanism of 24-OH-panaxadiol
10.13422/j.cnki.syfjx.20190622
- VernacularTitle: 24-羟基-人参二醇的抗癌作用及基于分子对接的机制
- Author:
Qian ZHENG
1
;
Zhao-hui WANG
2
;
Zeng QI
3
;
Ping-ya LI
3
Author Information
1. Shanxi Medical University, Taiyuan 030001, China
2. Center for Transplantation Sciences, Massachusetts General Hospital and Harvard Medical School, Boston 02129, USA
3. School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China
- Publication Type:Research Article
- Keywords:
ginsenoside;
anticancer;
docking;
24-OH-panaxadiol
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2019;25(6):81-88
- CountryChina
- Language:Chinese
-
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 (P<0.05) in a dose-dependent manner. In the molecular docking test, 24-OH-PD was docked successfully with 11 tumor related proteins, including purine nucleoside phosphorylase (PNP), protein tyrosine kinase, protein kinase C (PKC), B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-xl (Bcl-xl) and Caspase-8 et al, which demonstrated that the anti-tumor effect of 24-OH-PD may be related to the direct effects on these proteins. Conclusion: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.