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Cancer Chemoprevention by Dietary Compounds Targeting Angiogenesis

Cancer remains a leading cause of death worldwide. Due to angiogenesis and metastatic potency of cancer, chemotherapies are not adequate for metastatic tumor. We investigated anti-carcinogenic effects of resveratrol in comparison to those of pterostilbene in colon cancer cells. We found superior activities of pterostilbene over resveratrol in growth inhibition as well as apoptosis induction. Higher Intracellular concentration of pterostilbene could contribute to its higher potency in anti-carcinogenesis; however, both resveratrol and pterostilbene failed to inhibit colon cancer cell migration in vitro. Polymethoxylatedflavones (PMFs) found exclusively in citrus fruits have shown inhibitory effects against cancer. We investigated their anti-angiogenic activities in endothelial cells as well as anti-metastatic in lung cancer cells. PMFs inhibited endothelial cells migration and tube formation with higher potency found in 5-hydroxylated PMFs and their metabolites. We discovered that their inhibition is correlates well with their ability to interfere with cellular signaling between tumor cell and endothelial cells. In lung cancer cells, PMFs inhibited cell migration and cell invasion. They modulate angiogenesis/metastasis related proteins. PMFs suppressed cell migration by down regulating upstream regulator and signaling molecule which control migration. They inhibit cell invasion by disrupting upstream regulator molecules and inhibiting enzymes expression while inducing endogenous enzyme inhibitor. The intracellular contents of 5-hydroxylated PMFs and metabolites were also investigated and they partially explain the different magnitude of anti-angiogenesis/metastasis among the PMFs compound.