The pro-apoptotic activity of sinueracasbanone D isolated from Sinularia Leptoclados in hepatocellular carcinoma cells

The soft-bodied corals of the genera Sarcophyton and Sinularia (Alcyoniidae) are known as a warehouse of casbane and cembranoid diterpenoids with remarkable antitumor effects. Two casbane-type diterpenoids (1, 2) along with four cembrane-type diterpenoids (3-6) were isolated from the diethyl ether soluble fraction of the organic extracts of the Red Sea soft corals Sinularia leptoclados and Sarcophyton glaucum, respectively. The antiproliferative activity of all isolated compounds (1-6) against three hepatocellular carcinoma cells, namely, Huh-7, SNU 499, and HepG2, along with the normal cells EA.hy 926, was evaluated. Sinueracabanone D (1) displayed a remarkable antiproliferative effect against the examined cancer cell lines, especially HepG2 cells with IC50 of 4.0 +/- 0.37 mu M. Cell cycle analysis indicated compound 1 caused the accumulation of HepG2 cells in the G2/M-phase. Further, compound 1 exhibited significant pro-apoptotic activities in HepG2 cells as evidenced by annexin V staining, enhanced mRNA expression of Bax, cytochrome C, and caspase 3, as well as inhibition of Bcl2 expression. Also, challenging HepG2 cells with sinueracabanone D (1) enhanced the active oxygen species generation and decreased mitochondrial membrane potential. In conclusion, compound 1 possesses potent antiproliferative activities against HepG2 cells. These antiproliferative activities are mediated, at least partly, by their ability to induce apoptosis, mitochondrial dysfunction, and oxidative stress.