Steroidal Constituents from the Edible Sea Urchin Diadema savignyi Michelin Induce Apoptosis in Human Cancer Cells

Abstract

Bioassay-directed fractionation and purification were used to isolate 12 steroids (1–12) from a CH₂Cl₂ extract of the edible Vietnamese sea urchin Diadema savignyi Michelin. The cytotoxic activity of the CH₂Cl₂ extract and 12 steroids was evaluated in three human cancer cell lines (HL-60, PC-3, and SNU-C5). Relative to the effects of the positive control, mitoxantrone, the CH₂Cl₂ extract (with an inhibitory concentration of 50% [IC₅₀] values ranging from 1.37±0.15 to 3.11±0.15 μg/mL) and compounds 2 (with IC₅₀ values ranging from 5.29±0.11 to 6.80±0.67 μM) and 11 (with IC₅₀ values ranging from 4.95±0.07 to 6.99±0.28 μM) exhibited potent cytotoxic effects against all three tested human cancer cell lines. In addition, the CH₂Cl₂ extract and compounds 2 and 11 were found to induce apoptosis. The induction of apoptosis was accompanied by alterations of the apoptosis-related protein expression, inactivation of ERK1/2 mitogen-activated protein kinase signaling, and decreased c-Myc expression. These data suggest that compounds 2 and 11 from the edible sea urchin D. savignyi may have potential for the treatment of colon cancer, leukemia, and prostate cancer as complementary cancer remedies.