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 IC 50 of 4.0 ± 0.37 µM. 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.