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.
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Authors | Masuko Kobori, Mitsuru Yoshida, Mayumi Ohnishi-Kameyama, Toshiyuki Takei, Hiroshi Shinmoto |
Journal | Biological & pharmaceutical bulletin
(Biol Pharm Bull)
Vol. 29
Issue 4
Pg. 755-9
(Apr 2006)
ISSN: 0918-6158 [Print] Japan |
PMID | 16595913
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibiotics, Antineoplastic
- Sterols
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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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