Steroidal Constituents from the Starfish Astropecten polyacanthus 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 CH₂Cl₂ fraction and compound 7 exhibit potent cytotoxic effects against HL-60 human leukemia cells with the IC₅₀ of 8.29 µg/mL and 2.70 µM, respectively, comparing to the positive control, mitoxantrone (IC₅₀=6.80 µM). When HL-60 cells were treated with the CH₂Cl₂ 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 CH₂Cl₂ 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 CH₂Cl₂ 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 CH₂Cl₂ 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 CH₂Cl₂ fraction and compound 7 for leukemia treatment.