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Previous studies have suggested that Citrus fruits might suppress the proliferation of various cancer cells. However, little is known about any specific ingredients in the extract of Citrus fruits to exert its anti-proliferative activity in cancer cells. The present study aimed to identify the active ingredients in Citrus fruits to suppress the proliferation of rat hepatocellular carcinoma cells. Among tested compounds, two polymethoxylated flavones (nobiletin and tangeritin) showed significant anti-proliferative activity whereas other compounds (synephrine, rutin, hesperidin) did not. Interestingly, nobiletin as well as tangeritin also decreased the protein amount of gluconeogenic enzymes, PEPCK and G6Pase. The possible involvement of gluconeogenic activity in the proliferation of hepatocellulacarcinoma cells are further to be investigated.
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