Abstract
BackgroundFlavonoids are structurally heterogeneous, polyphenolic compounds present in high concentrations in fruits, vegetables, and other plant-derived foods. Currently, there is growing interest in the therapeutic applications of bioflavonoids for the treatment and prevention of diseases in humans. Myricetin is a naturally occurring flavonoid that is commonly found in tea, berries, fruits, vegetables, and medicinal herbs. Previous studies have shown that myricetin has antioxidant, anti-inflammatory and potent anticancer effects. It was interesting to investigate whether myricetin has the cooperative inhibitory effect combined with 5-fluorouracil on esophageal cancer cells.MethodsEC9706 cells were treated with 5-fluorouracil combination with or without myricetin. Colony formation assays, CCK-8 assay and flow cytometry were used to evaluate the chemosensitization activity of myricetin combine with 5-fluorouracil on the cell growth and viability, cell proliferation and apoptosis in vitro. Western blot was engaged to detect changes of Survivin, Cyclin D, Bcl-2, Caspase-3 and P53 protein expression level, which were associated with cells proliferation and apoptosis. Nude mouse tumor xenograft model was built to assessed chemosensitization effect of myricetin combine with 5-fluorouracil in vivo.ResultsCompared with the 5-fluorouracil group without myricetin treatment, the groups treated with 5-fluorouracil combine with myricetin showed significantly suppressed cell survival fraction and proliferation, increased the cell apoptosis. Decreased Survivin, Cyclin D, Bcl-2, and increased Caspase-3, P53 expression level were aslo confirmed by western blot in 5-fluorouracil combine with myricetin groups in vitro. And in vivo assay, growth speed of tumor xenografts was significantly decreased in the mice treated with 5-fluorouracil + myricetin combiantion group.ConclusionsThe study demonstrated both in vitro and in vivo evidence that combination of myricetin with 5-fluorouracil chemotherapy can enhance tumor chemosensitivity of esophageal cancer EC9706 cells, and myricetin could be a potential chemosensitizer for esophageal cancer therapy.
Highlights
Esophageal cancer is a global health problem that ranked eighth in terms of incidence and sixth in terms of mortality [1,2]
EC9706 cell were plated into 6-well plates and exposed to different concentration of myricetin, After 4 hours later, 5-FU (10 μM, 20 μM, 40 μM, 80 μM, 160 μM) was added into the culture and maintained for 48 hours. 48 hours later, all cells were washed, trypsinized, counted, and plated into 10 cm dishes containing DMEM supplemented with 10% FCS until colony formation was visible, which usually occurred in approximately 10-14 days
It was found that treatment of the EC9706 cells with different concentration 5-FU alone could lead to inhibition effect on clonogenic survival
Summary
Esophageal cancer is a global health problem that ranked eighth in terms of incidence and sixth in terms of mortality [1,2]. Systemic chemotherapy is regarded as one of the most effective treatments to improve survival [5,6,7]. The toxicity of most chemotherapy agents to normal tissues was the main obstacle to successful treatment. There is growing interest in the therapeutic applications of bioflavonoids for the treatment and prevention of diseases in humans. Myricetin is a naturally occurring flavonoid that is commonly found in tea, berries, fruits, vegetables, and medicinal herbs. It was interesting to investigate whether myricetin has the cooperative inhibitory effect combined with 5-fluorouracil on esophageal cancer cells
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