Effect of structural analogues of propionate and butyrate on colon cancer cell growth.
The aim of this study was to evaluate the effects of natural short-chain fatty acids (butyrate, propionate, valerate, acetate) and structural analogues of butyrate and propionate on cell growth and apoptosis in three human colonic adenocarcinoma cell lines (HT-29, Colo-320, and SW-948). We have previously shown that mercapto- and bromo-analogues of butyrate and propionate compete with natural short-chain fatty acids for uptake in the colonocyte. Among naturally occurring short-chain fatty acids, butyrate was the most potent inhibitor of proliferation in all three cell lines. Propionate exhibited a weaker antiproliferative effect, while other short-chain fatty acids (valerate, acetate) were ineffective. Bromo-analogues of butyrate and propionate were more potent proapoptotic agents than butyrate. In contrast to butyrate, the analogues induced strand breaks on isolated supercoiled DNA, the effect being completely reversed by a DNA-protecting agent, spermine. We conclude that bromo-analogues of butyrate and propionate are more potent proapoptotic agents than butyrate in colon cancer cells in culture. Their effect may be a result of direct DNA damage.
Milovic
V
V
2nd Department of Medicine, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Teller
I C
IC
Turchanowa
L
L
Caspary
W F
WF
Stein
J
J
D000230:Adenocarcinoma / Q000188:drug therapy*; D017209:Apoptosis / Q000187:drug effects; D001966:Bromine / Q000737:chemistry; D002087:Butyrates / Q000737:chemistry* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004249:DNA Damage / Q000187:drug effects; D004278:DNA, Superhelical / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000494:pharmacology; D006801:Humans; D010957:Plasmids / Q000378:metabolism; D011422:Propionates / Q000737:chemistry* / Q000494:pharmacology*; D013096:Spermine / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D002087:Butyrates; D004278:DNA, Superhelical; D005227:Fatty Acids; D011422:Propionates; D013096:Spermine; D001966:Bromine