IGF-II down regulation associated cell cycle arrest in colon cancer cells exposed to phenolic antioxidant ellagic acid.
Altered cell and tissue differentiation is characteristic of premalignant lesions long before they become invasive and metastatic. One approach to controlling preneoplastic lesions is to block their expansion with non-toxic agents that suppress cell proliferation and induce apoptosis. Here, we show that ellagic acid, a natural, dietary phenolic antioxidant when given at 10(-5) M for 48 hours to colon cancer cells (SW 480), induced down regulation of insulin like growth factor IGF-II, activated p21(waf1/Cip1), mediated a cumulative effect on G1/S transition phase and caused apoptotic cell death. SW480 colon cancer cells expressed significant mRNA levels for the mitogenic insulin like growth factor (IGF-II). Collectively, these observations suggest that growth inhibition by ellagic acid is mediated by signaling pathways that mediate DNA damage, triggers p53, which in turn activates p21 and at the same time alters the growth factor expression, resulting in the down regulation of IGF-II.
Narayanan
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American Health Foundation, 1, Dana Road Valhalla, NY 10595, USA. bhagavat@earthlink.net
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D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000648:ultrastructure; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis; D015536:Down-Regulation; D004610:Ellagic Acid / Q000494:pharmacology*; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
D000975:Antioxidants; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D004610:Ellagic Acid; D007335:Insulin-Like Growth Factor II