Steroidal Constituents from the Starfish <i>Astropecten polyacanthus</i> and Their Anticancer Effects

Abstract

Using various chromatographic methods, four new steroids, astropectenols A-D (1-4), along with three known compounds (5-7) were isolated from a methanol extract of the starfish Astropecten polyacanthus. The structure elucidation was confirmed by spectroscopic methods, including one dimensional (1D)-, 2D-NMR and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). The CH 2 Cl 2 fraction and compound 7 exhibit potent cytotoxic effects against HL-60 human leukemia cells with the IC 50 of 8.29 µg/mL and 2.70 µM, respectively, comparing to the positive control, mitoxantrone (IC 50 6.80 µM). When HL-60 cells were treated with the CH 2 Cl 2 fraction or compound 7, several apoptosis events like chromatin condensation and the increase of the population of sub-G1 hypodiploid cells were observed. Investigations for the possible mechanism underlying the induction of apoptosis showed that CH 2 Cl 2 fraction or compound 7 induced apoptosis through down-regulation of Bcl-2, up-regulation of Bax, cleavage of caspase-9, cleavage of caspase-3 and cleavage of poly(ADP-ribose) polymerase (PARP) in HL-60 cells. Furthermore, the apoptosis induction of HL-60 cell by CH 2 Cl 2 fraction or compound 7 was attended by the decreasing of phospho-extracellular signal-regulated kinase (ERK) 1/2 and C-myc. These results indicated that the CH 2 Cl 2 fraction and compound 7 could induce the apoptosis of HL-60 cells via the inactivation of ERK 1/2 and the decrease of C-myc. Our finding suggested the potential using of the CH 2 Cl 2 fraction and compound 7 for leukemia treatment. Key words Astropecten polyacanthus; starfish; oxygenated steroid; cytotoxic; apoptosisEchinoderms represent an outstanding source of polar steroids of a great structural diversity, showing various biological activities. Among five living classes of the phylum Echinodermata, two classes Asteroidea (starfish) and Ophiuroidea (brittle stars) are especially rich in polar steroids.1) The research on starfish has expanded rapidly over the past few years, which has been prompted by the discovery of a variety of unique structures and the interest in their pharmacological properties. Starfish have attracted organic chemists, biochemists, and pharmacologists as a fascinating source of bioactive marine natural products, especially steroids and steroidal glycosides. 2)Some polyhydroxylated steroids from starfish exhibited antibacterial and cytotoxic activities. 1)In our screening research for anti-cancer agents from Vietnamese echinoderms, we found the starfish Astropecten polyacanthus to possess significant cytotoxic effects. As part of our continuing investigations on this starfish, we report herein the isolation, structural elucidation, and evaluation of anticancer activity of extracts and seven steroids, including four new compounds 1-4, from the starfish A. polyacanthus.

Anti-Inflammatory Components of the Starfish Astropecten polyacanthus

“…Astropecten species are abundant in the Vietnamese sea, and have been used as tonic agents in Vietnamese folk medicine. In previous studies, we isolated and identified seven steroids ( 1 – 7 ) from A. polyacanthus (Figure 1), some of which had cytotoxic effects against HL-60 (leukemia), PC-3 (prostate), and SNU-C5 (colorectal) human cancer cells [17]. In continuation of our investigations on Vietnamese marine organisms regarding anti-inflammatory activity [18,19,20,21], we found that the MeOH extract and CH 2 Cl 2 partition showed significant in vitro anti-inflammatory activities.…”

Asterosaponins from the Starfish <i>Astropecten monacanthus</i> Suppress Growth and Induce Apoptosis in HL-60, PC-3, and SNU-C5 Human Cancer Cell Lines

“…To date, no investigations of their biological activities have been reported. In the course of our search for new biologically active compounds from Vietnamese starfish, [8][9][10] six asterosaponins, astrosteriosides A-D (1-3 and 5), psilasteroside (4), and marthasteroside B (6), were recently isolated from the starfish A. monacanthus ( Fig. 1) and their anti-inflammatory effects were evaluated.…”

Naturally occurring marine α,β‐epoxy steroids: Origin and biological activities

“…The steroids exhibited moderate cytotoxicity and inhibitory activity against phospholipase A2. [58] Rare steroid, cytotoxic astropectenol C (46) with 8,9-epoxy group was obtained from a methanol extract of the starfish Astropecten polyacanthus, [59] and (3,5,7,8,14,24R)-7,8-Epoxy-14-methoxy-4-methyleneergostan-3-ol (47) was obtained from sponge Theonella swinhoei. [60] The cytotoxic polyoxygenated sterols, homaxisterols B1 (48) and B2 (49) have been isolated from the MeOH extract of the marine sponge Homaxinella sp.…”