Perturbation of polyamine metabolism and its relation to cell death in human colon cancer cells treated by 7beta-hydroxycholesterol and 7beta-hydroxysitosterol.
7beta-OHsitosterol and 7beta-OHcholesterol are natural compounds of plant and animal cells with high structural similarity. Recently it was reported that both compounds induced apoptosis on human colon cancer cells by targeting different signalling pathways. Our study aimed at comparing their effects on polyamine metabolism and its relation to apoptosis. When human colon cancer cells were exposed to 7beta-OHsitosterol and to 7beta-OHcholesterol at concentrations inhibiting growth by the same degree, both compounds caused a reduction of polyamine biosynthetic enzyme activity, of the polyamine pools, and an increase of N1-acetylspermidine concentration indicating the enhancement of polyamine catabolism. Exogenous putrescine did not prevent cell death caused by 7beta-OHsitosterol, whereas 7beta-OHcholesterol-induced apoptosis was inhibited. MDL 72527, an inhibitor of polyamine oxidase, an enzyme of the polyamine catabolic pathway, potentiated the antiproliferative effects of 7beta-OHcholesterol by increasing the N1-acetylspermidine pool and enhanced the accumulation of apoptotic cells. In contrast, MDL 72527 did not change the apoptosis rate and the N1-acetylspermidine content in cells treated with 7beta-OHsitosterol. These data indicate that polyamine metabolic perturbations triggered by 7beta-OHcholesterol but not by 7beta-OHsitosterol are related to cell death.
Roussi
Stamatiki
S
INSERM U682, Université Louis-Pasteur EA3430, Faculté of Médecine, Laboratoire de Prévention Nutritionnelle du Cancer, IRCAD, 67092 Strasbourg, France.
Gossé
Francine
F
Aoudé-Werner
Dalal
D
Zhang
Xin
X
Geoffroy
Philippe
P
Miesch
Michel
M
Marchioni
Eric
E
Raul
Francis
F
D015317:Biogenic Polyamines / Q000737:chemistry / Q000378:metabolism*; D018938:Caco-2 Cells; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D048708:Cell Growth Processes / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D011700:Putrescine / Q000031:analogs & derivatives / Q000494:pharmacology; D012855:Sitosterols / Q000494:pharmacology*; D013095:Spermidine / Q000031:analogs & derivatives / Q000494:pharmacology
D015317:Biogenic Polyamines; D006888:Hydroxycholesterols; D012855:Sitosterols; C017988:N(1)-acetylspermidine; C044445:MDL 72527; C011486:hydroxysitosterol; C011724:cholest-5-en-3 beta,7 alpha-diol; D013095:Spermidine; D011700:Putrescine