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Research Article

5-Hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone, a polymethoxyflavone, exerts antitumor effect on PI3K/Akt signaling pathway in human gastric cancer cell BGC-7901

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Pages 471-477 | Received 15 Oct 2015, Accepted 16 Nov 2015, Published online: 16 Dec 2015
 

Abstract

5-Hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone (5HHMF), a polymethoxyflavone (PMF) mainly found in citrus plants, exhibits excellent physiological functions. In this study, we aimed to investigate the anticancer activity of 5HHMF against human gastric cancer cell BGC-7901 both in vitro and in vivo and illustrate the potential mechanisms. The proliferation of BGC-7901 cells was assessed by MTT assay. Reactive oxygen species (ROS) level was determined by ELISA kit. The protein expression was determined by western blot analysis. Antitumor activity of 5HHMF in vivo was evaluated in BALB/c nude mice. The results showed that treatment with 5HHMF significantly suppressed BGC-7901 cells proliferation, increased ROS generation, and upregulated cytochrome c release from the mitochondria to the cytosol. Western blot analysis demonstrated that 5HHMF significantly downregulated the expression of procaspase-3, procaspase-9, and PARP and upregulated cleaved caspase-3, cleaved caspase-9, cleaved PARP, and Bax/Bcl-2 ratio. Meanwhile, 5HHMF treatment markedly decreased the expression of PI3K and p-Akt. In addition, 5HHMF effectively inhibited tumor growth in xenograft models in BALB/c nude mice without major side action. In summary, 5HHMF-induced apoptosis via targeting PI3K/Akt, indicating 5HHMF is a potential antitumor agent for gastric cancer.

Declaration of interest

There are no conflicts of interest. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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