Transformation of ergosterol peroxide to cytotoxic substances by rat intestinal bacteria.
Ergosterol peroxide (EPO, 1) is a major antitumor sterol produced by edible or medicinal mushrooms. Following oral administration of 1 to rats or anaerobic in vitro incubation of 1 with rat fecal bacteria, three metabolites were detected and their structures were identified to be 5alpha,6alpha-epoxyergosta-8(14),22-diene-3beta,7alpha-diol (M1, 2), 5alpha,6alpha-epoxyergosta-8,22-diene-3beta,7alpha-diol (M2, 3), and 5alpha,6alpha-epoxy-3beta-hydroxyergosta-22-ene-7-one (M3, 4) by spectroscopic analysis. Of these, M2 and M3 showed more potent inhibitory activity than the original compound 1 against proliferation of CACO-2, WiDr, DLD-1 and Colo320 human colorectal adenocarcinoma cells. These findings suggest that bacterial metabolites of EPO play a significant role in its cytotoxic activity against human colorectal cancer cells.
Lee
Joo-Sang
JS
Division of Metabolic Engineering, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Ma
Chao-Mei
CM
Park
Dong-Ki
DK
Yoshimi
Yasuharu
Y
Hatanaka
Minoru
M
Hattori
Masao
M
D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D003603:Cytotoxins / Q000378:metabolism*; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000378:metabolism; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051381:Rats
D003603:Cytotoxins; C036071:ergosterol-5,8-peroxide; D004875:Ergosterol