Steroids from the Cold Water Starfish Ctenodiscus crispatus with Cytotoxic and Apoptotic Effects on Human Hepatocellular Carcinoma and Glioblastoma Cells

Abstract

Chemical investigation on the methanol extract of the starfish Ctenodiscus crispatus resulted in the isolation of five steroids, (22E,24ξ)-26,27-bisnor-24-methyl-5α-cholest-22-en-3β,5,6β,15α,25-pentol 25-O-sulfate (1), (22E,24R,25R)-24-methyl-5α-cholest-22-en-3β,5,6β,15α,25,26-hexol 26-O-sulfate (2), (28R)-24-ethyl-5α- cholesta-3β,5,6β,8,15α,28,29-heptaol-24-sulfate (3), (25S)-5α-cholestane-3β,5,6β,15α,16β,26-hexaol (4), and Δ7-sitosterol (5). Their structures were identified by extensive spectroscopic analyses, including 1D, 2D NMR and MS and chemical methods. Compound 4 showed cytotoxicity against human hepatoma HepG2 and glioblastoma U87MG cells via inhibition of cell growth and induction of apoptosis. Induction of apoptosis by 4 was demonstrated by cell death, DNA fragmentation, increased Bax/Bcl-2 protein ratio and the activation of caspase-3, caspase-9 and poly (ADP-ribose) polymerase (PARP).