5α,8α-epidioxy-22E-ergosta-6,9(11),22-trien-3β-ol from an edible mushroom suppresses growth of HL60 leukemia and HT29 colon adenocarcinoma cells

We purified a sterol with antitumor activity from the edible mushroom Sarcodon asprants (BERK.) S. ITO and identified it as 5 alpha,8 alpha-epidioxy-22E-ergosta-6,9(11),22-trien-3 beta-ol (9,11-dehydroergosterol peroxide (9(11)-DHEP)). Purified 9(11)-DHEP was a more effective inhibitor of HL60 leukemia cell growth and stronger apoptosis-inducer than 5 alpha,8 alpha-epidioxy-22E-ergosta-6,22-dien-3 beta-ol (ergosterol peroxide (EP)) that we had previously identified as an apoptosis inducer. Moreover, 9(11)-DHEP selectively suppressed the growth of HT29 human colon adenocarcinoma cells but: not WI38 normal human fibroblasts. After 5d incubation of HT29 with 7 mu m 9(11)-DHEP, the number of S phase cells decreased from 23 to 15% of total diploid cells and 17% became hypodiploid. Expression of the cyclin-dependent kinase inhibitor 1A (p21, WAF1, Cip1) (CDKN1A), which has been shown to cause cell cycle arrest and apoptosis in HT29 cells, was induced by 9(11)-DHEP. These results suggest that 9(11)-DHEP inhibits HT29 cell growth by inducing CDKN1A expression, thus causing cell cycle arrest and apoptosis.