Perturbation of polyamine metabolism and its relation to cell death in human colon cancer cells treated by 7β-hydroxycholesterol and 7β-hydroxysitosterol

摘要

7β-OHsitosterol and 7β-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 7β-OHsitosterol and to 7β-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 7β-OHsitosterol, whereas 7β-OHcholesterol-induced apoptosis was inhibited. MDL 72527, an inhibitor of polyamine oxidase, an enzyme of the polyamine catabolic pathway, potentiated the antiproliferative effects of 7β-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 7β-OHsitosterol. These data indicate that polyamine metabolic perturbations triggered by 7β-OHcholesterol but not by 7β-OHsitosterol are related to cell death.