Inhibitory Effects of 5-Demethyltangeretin and 5-Acetyloxy-6,7,8,4′-tetramethoxyflavone on Human Colon Cancer Cells

Abstract

Tangeretin (5,6,7,8,4′-pentamethoxyflavone, TAN), a natural polymethoxyflavone (PMF) present in citrus fruits, is reported to have several biological functions. Our previous studies show that demethylation at the C5 group of PMFs resulted in more potent anti-cancer property. In this study, we prepared an acetylated TAN (5-ATAN) with an acetyl group at C5 position to replace 5-methyl group of tangeretin and compared the anti-proliferative activities of TAN, 5-demethyl TAN (5-DTAN) and 5-ATAN. We found that all the PMFs caused significant cytotoxicity effect in human colon cancer HCT116 and HT-29 cells. Treatment of HCT116 cells with TAN, 5-DTAN and 5-ATAN resulted in G2/M phase cell cycle arrest while 5-DTAN and 5-ATAN also triggered apoptosis but not TAN. Cleavage of caspase-3 and increased p53 protein expression observed in 5-DTAN and 5-ATAN-treated HCT116 cells suggested the apoptosis-dependent mechanism. Moreover, 5-ATAN exhibited a more effective anti-proliferative and apoptosis-inducing effect than 5-DTAN in HT-29 cells. Interestingly, cell cycle arrest at S and G2/M phase were found in 5-ATAN treated HT-29 cells whereas 5-DTAN only caused G2/M phase arrest. These results suggest that 5-DTAN and 5-ATAN could be effective anti-cancer agents.

An insight into the role of citrus bioactives in modulation of colon cancer

“…The authors suggested that these effects could be due to the additive or synergistic effects of phytochemicals present in gold lotion (Lai et al, 2013a). Lai et al (2013b) investigated the effect of demethylation and acetylation at C5 position of tangeretin (TAN) structure on its anticancer action in HCT116 and HT29 cells. It was found that TAN and both its derivatives i.e.…”

Blockade of STAT3 Signaling Contributes to Anticancer Effect of 5-Acetyloxy-6,7,8,4′-Tetra-Methoxyflavone, a Tangeretin Derivative, on Human Glioblastoma Multiforme Cells

“…5-acetyloxy-6,7,8,4′-tetramethoxyflavone (5-AcTMF) is an acetylation-modified derivative of Tangeretin which improves in vivo bioavailability and efficacy [19,24]. It is worth noting that 5-AcTMF has been demonstrated to exert in vitro or in vivo anticancer activity against a wide range of human cancers, including breast, colon, lung, and multiple myeloma [24,25,26,27]. However, the anticancer effect of 5-AcTMF on GBM has not been previously addressed.…”