5alpha,8alpha-Epidioxy-22E-ergosta-6,9(11),22-trien-3beta-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 aspratus (BERK.) S. ITO and identified it as 5alpha,8alpha-epidioxy-22E-ergosta-6,9(11),22-trien-3beta-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 5alpha,8alpha-epidioxy-22E-ergosta-6,22-dien-3beta-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 5 d incubation of HT29 with 7 microM 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.
Kobori
Masuko
M
National Food Research Institute, Tsukuba, Ibaraki, Japan. kobori@nfri.affrc.go.jp
Yoshida
Mitsuru
M
Ohnishi-Kameyama
Mayumi
M
Takei
Toshiyuki
T
Shinmoto
Hiroshi
H
D000363:Agaricales / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004171:Diploidy; D005347:Fibroblasts / Q000187:drug effects; D018922:HL-60 Cells; D019073:HT29 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase / Q000187:drug effects; D013261:Sterols / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D013261:Sterols