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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.

Abstract
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.
AuthorsMasuko Kobori, Mitsuru Yoshida, Mayumi Ohnishi-Kameyama, Toshiyuki Takei, Hiroshi Shinmoto
JournalBiological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 29 Issue 4 Pg. 755-9 (Apr 2006) ISSN: 0918-6158 [Print] Japan
PMID16595913 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibiotics, Antineoplastic
  • Sterols
Topics
  • Agaricales (chemistry)
  • Antibiotics, Antineoplastic (isolation & purification, pharmacology)
  • Apoptosis (drug effects)
  • Cell Cycle (drug effects)
  • Chromatography, High Pressure Liquid
  • Diploidy
  • Fibroblasts (drug effects)
  • HL-60 Cells
  • HT29 Cells
  • Humans
  • Magnetic Resonance Spectroscopy
  • Reverse Transcriptase Polymerase Chain Reaction
  • S Phase (drug effects)
  • Sterols (metabolism)

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