New Diterpene Compound from Euphorbia connate Boiss., 3,7,14,15-Tetraacetyl-5-Propanoyl-13(17)-Epoxy-8,10(18)-Myrsinadiene, Inhibits the Growth of Ovarian Cancer Cells by Promoting Mitochondrial-Mediated Apoptosis

Abstract

Ovarian cancer due to the difficulties in early clinical diagnosis and absence of successfull treatment has poor prognosis and high mortality among all gynecological malignancies. Many evidence has revealed that plants of the Euphorbiaceae family are precious sources of novel bioactive compounds with anti-tumor activities. 3,7,14,15-tetraacetyl-5-propanoyl-13(17)-epoxy-8,10(18)-myrsinadiene (TPEM) is a new myrsinane-type diterpene isolated recently by our group from aerial parts of Euphorbia Connata and the present study was aimed to explore its inhibitory effects on growth of two human ovarian cancer cells, OVCAR-3, and Caov-4. The obtained results indicated that growth of OVCAR-3 and Caov-4 cells was significantly inhibited by TPEM in a dose-dependent manner, with the IC50 values of 41.27 ± 1.52 and 36.44 ± 2.41 µM, respectively. Furthermore, using Annexin V-FITC and PI staining it was confirmed that the induced cell death was mainly mediated through apoptotic pathway. Further observations such as decrease in the mitochondrial membrane potential (ΔΨm), increase in the activity of caspase-3 and elevation of the Bax/Bcl-2 ratio suggested the role of mitochondria in the induction of apoptosis by TPEM. ROS level was also remarkably increased in OVCAR-3 and Caov-4 cells in response to TPEM treatment. In conclusion, these findings provide first evidences about potential anticancer properties of TPEM.