Cytotoxic and Pro-Apoptotic Activities of Diterpenoids from Zhumeria Majdae

Since the ethylacetate (EtOAc) extract of the roots of Zhumeria majdae had the potent cytotoxic effect (IC50 < 50 mu g/ml) on three cancer cell lines; MCF-7, PC3 and MDA-MB-231, therefore the purpose of this study was the isolation of the responsible cytotoxic compounds from the plant. Isolation of the extract led to the identification of four diterpenoids named as lanugon Q (1), 12,16-dideoxy aegyptinone B (2), 12-deoxy-salvipisone (3) and manool (4). The chemical structures have been determined on the basis of 1D and 2D NMR experiments. Compound 1 is reported for the first time in the plants of the Zhumeria genus. The results of cytotoxic and apoptotic evaluation revealed that compound 2 had a strong cytotoxic effect with the IC50 value of 15.90 mu g/ml against MCF-7 cell lines. The sub-G1 peak in flow cytometry histogram of cells treated with the EtOAc extract and compound 2 showed the induction of apoptosis. Changes in the Bax/Bcl-2 ratio and cleavage of PARP were observed. It is to be noted that owing to the strong cytotoxic effect, the Z. majdae extract could be represented as a therapeutic agent against cancer.