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The Flavonol Isorhamnetin Exhibits Cytotoxic Effects on Human Colon Cancer Cells

AuthorsJaramillo Carmona, S. ; López, Sergio ; Varela, Lourdes; Rodríguez-Arcos, Rocío ; Jiménez Araujo, Ana ; Abia, Rocío ; Guillén Bejarano, Rafael ; Muriana, Francisco J. G.
Cell growth
Cell cycle
Colon cancer
Issue Date5-Oct-2010
PublisherAmerican Chemical Society
CitationJournal of Agricultural and Food Chemistry 58(20): 10869-10875 (2010)
AbstractThe aim of this study was to determine whether isorhamnetin, an immediate 3′-O-methylated metabolite of quercetin, affects proliferation, cell death, and the cell cycle of human colon carcinoma (HCT-116) cells. Isorhamnetin was found to be a potent antiproliferative agent in a dose- and time-dependent manner, with an IC50 of 72 μM after 48 h of incubation as estimated by MTT assay. Flow cytometry and fluorescence microscopy analysis showed that isorhamnetin exerted a stimulatory effect on apoptosis and necrosis. Isorhamnetin also increased the number of cells in G2/M phase. Serum deprivation appeared to potentiate the effects of isorhamnetin on cell death and facilitated cell cycle progression to G0/G1 phase. These results suggest that isorhamnetin might mediate inhibition of HCT-116 cell growth through the perturbation of cell cycle progression and are consistent with the notion that G2/M checkpoints could be a conserved target for flavonoids in human colon cancer cells, leading to apoptotic and necrotic death. These antiproliferative, apoptotic, necrotic, and cell cycle effects suggest that isorhamnetin may have clinically significant therapeutic and chemopreventive capabilities. To our knowledge, this is the first report of the effect of isorhamnetin on human colon cancer cells.
Publisher version (URL)http://dx.doi.org/10.1021/jf102669p
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