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).

Bioactive Compounds with Antiglioma Activity from Marine Species

“…Five structurally close steroid compounds namely 22E,24ξ)-26,27-bisnor-24-methyl-5α-cholest22-en-3β,5,6β,15α,25-pentol 25-O-sulfate, (22E,24R,25R)-24-methyl-5α-cholest-22-en-3β,5,6β,15α,25,26-hexol 26-O-sulfate, (28R)-24-ethyl-5α-cholesta-3β,5,6β,8,15α,28,29-heptaol-24-sulfate, Δ7-sitosterol, and (25S)-5α-cholestane-3β,5,6β,15α,16β,26-hexaol were isolated from the methanol extract of the starfish Ctenodiscus crispatus and investigated for their antiglioma activity [ 139 ]. Only the latter compound, which structure is presented on Figure 13 , have shown significant dose-dependent cytotoxicity in a range of concentrations 50, 100, and 200 μM against glioblastoma U87MG cells via inhibition of cell growth and apoptosis induction.…”

“…The ratio of Bax/Bcl-2 exhibited a dose-dependent increase in the U87MG cells. The treatment with this steroid significantly increased the cleavage of caspase-3, caspase-9, and poly (ADP-ribose) polymerase (PARP) in a dose-dependent manner [ 139 ]. Thus, anti-glioblastoma effects of active steroids were mediated through the apoptotic process.…”

Bioactive Compounds With Antiglioma Activity From Marine Species

“…Five structurally close steroid compounds namely 22E,24ξ)-26,27-bisnor-24-methyl-5α-cholest22-en-3β,5,6β,15α,25-pentol 25-O-sulfate (the molecular formula C26H43O8S¯), (22E,24R,25R)-24-methyl-5α-cholest-22-en-3β,5,6β,15α,25,26-hexol 26-O-sulfate, (28R)-24ethyl-5α-cholesta-3β,5,6β,8,15α,28,29-heptaol-24-sulfate (C29H51O10S¯), Δ7-sitosterol and (25S)-5α-cholestane-3β,5,6β,15α,16β,26-hexaol (C28H49O8) were isolated from the methanol extract of the starfish Ctenodiscus crispatus and investigated for their antiglioma activity [139]. Only the latter compound, which structure is presented on figure 13, have shown significant dose-dependent cytotoxicity in a range of concentrations 50, 100, and 200 μM against glioblastoma U87MG cells via inhibition of cell growth and apoptosis induction.…”

“…The structure of the steroid with anti-glioblastoma U87MG activity isolated from starfish Ctenodiscus crispatus [139].…”

Bright Spots in the Darkness of Cancer: A Review of Starfishes-Derived Compounds and Their Anti-Tumor Action

“…Quang and collaborators [70] isolated and identified five steroids from C. crispatus and investigated the biological potential of these compounds on two cell lines from human hepatocellular carcinoma (HepG2) and human glioblastoma (U87MG). Among the five, only one of these compounds, the (25S)-5α-cholestane-3β,5,6β,15α,16β,26-hexaol, showed relevant biological activity.…”