Dietary flavone is a potent apoptosis inducer in human colon carcinoma cells
Sommaire de l'article
Flavonoids are polyphenolic compounds that occur ubiquitously in plants. They are discussed to represent cancer preventive food components in a human diet that is rich in fruits and vegetables, To understand the molecular basis of the putative anticancer activity of flavonoids, we investigated whether and how the core structure of the flavones, 2-phenyl-4H-1-benzopyran-4-one (flavone) affects proliferation, differentiation, and apoptosis in HT-29 human colon cancer cells. Moreover, the effects of flavone in transformed epithelial cells were compared with those obtained in nontransformed primary mouse colonocytes. Proliferation, differentiation, and apoptosis in transformed as well as nontransformed colon cells were measured by fluorescence-based techniques, Apoptosis was also determined by changes in membrane permeability, FACScan analysis, and detection of DNA fragmentation. Semiquantitative reverse transcription PCR was performed to assess the effects of flavone on transcript levels. Flavone was found to reduce cell proliferation in HT-29 cells with an EC50 value of 54.8 +/- 1.3 µM and to potently induce differentiation as well as apoptosis, The flavonoid proved to be a stronger apoptosis inducer than the clinically established antitumor agent camptothecin. The effects of flavone in HT-29 cells were associated with changed mRNA levels of cell-cycle- and apoptosis-related genes including cyclooxygenase-2 (COX-2), nuclear transcription factor kappa B (NF-kappa B), acid bcl-X-L. Moreover, flavone, but not camptothecin, displayed a high selectivity for the induction of apoptosis and of growth inhibition only in the transformed colonocytes.In conclusion, the plant polyphenol flavone induces effectively programmed cell death, differentiation, and growth inhibition in transformed colonocytes by acting at the mRNA levels of genes involved in these processes, Because these genes play a crucial role in colon carcinogenesis, flavone may prove to be a potent new cytostatic compound with improved selectivity toward transformed cells.