A Study on the Chemo Preventive and Anticancer Potential of Dihydroxy Gymnemic triacetate Isolated From Gymnema sylvestre With Respect to Prostate Cancer.

Introduction: Prostate cancer is one of commonly diagnosed malignancies among men. Drugs from plant sources have gained much interest in treating this cancer due to their multi-functional, therapeutic properties and overall safety. Dihydroxy Gymnemic Triacetate (DGT) is a novel triterpenoid saponin isolated from Gymnema sylvestre proved for its antidiabetic activity was focused in the present study on analyzing its anticancer activity. The study aimed to evaluate the antagonist effect and drug like properties of DGT, against Bcl-2 and Bcl-XL protein through molecular docking and molecular dynamic studies. Method: To evaluate the cytotoxic potential and mode of action of DGT on PC-3 cells through cell proliferation assay, flow cytometry along with protein expression studies of Bcl-2, Bcl-XL, Mcl-1, Bad, Bax, Caspase 9 and Caspase 3. To assess chemopreventive effect of DGT in N-Methyl-N-nitrosourea (MNU) + Testosterone (T)-induced Sprague-Dawley male rats. Results: DGT effectively bound with Bcl-2 and Bcl-XL with good docking score and a stable docked complex throughout simulation period. DGT reduced the survival of PC-3 cells and showed accumulation of cells in the G2/M phase of the cell cycle. DGT was more potent in binding with anti-apopotic proteins, also satisfying Lipinski’s rule of five and ADME properties. Conclusion: DGT significantly acts on prostate cancer cells by activating apoptosis and did not exhibit any toxicity to the animal model. Hence, DGT could be considered for the preparation of chemopreventive agent and potent drug against prostate cancer. [ABSTRACT FROM AUTHOR]