Steroidal Constituents from the Starfish Astropecten polyacanthus and Their Anticancer Effects
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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 µ<span style="font-variant: small-caps;">M</span>, respectively, comparing to the positive control, mitoxantrone (IC50=6.80 µ<span style="font-variant: small-caps;">M</span>). 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.
- 公益社団法人 日本薬学会の論文
公益社団法人 日本薬学会 | 論文
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