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標題: Flavokawain B inhibits growth of human squamous carcinoma cells: Involvement of apoptosis and cell cycle dysregulation in vitro and in vivo
作者: Lin, E.
Lin, W.H.
Wang, S.Y.
Chen, C.S.
Liao, J.W.
Chang, H.W.
Chen, S.C.
Lin, K.Y.
Wang, L.
Yang, H.L.
Hseu, Y.C.
關鍵字: Flavokawain B;Cell cycle arrest;Apoptosis;KB cells;cancer cells;tumor-growth;death;mitochondria;expression;invasion;antioxidant;pathway;mice;bax
Project: Journal of Nutritional Biochemistry
期刊/報告no:: Journal of Nutritional Biochemistry, Volume 23, Issue 4, Page(s) 368-378.
Flavokawain B is a natural chalcone isolated from the rhizomes of Alpenia pricei Hayata. In the present study, we have investigated the antiproliferative and apoptotic effect of flavokawain B (5-20 mu g/ml; 17.6-70.4 mu M) against human squamous carcinoma (KB) cells. Exposure of KB cells with flavokawain B resulted in apoptosis, evidenced by loss of cell viability, profound morphological changes, genomic DNA fragmentation and sub-G1 phase accumulation. Apoptosis induced by flavokawain B results in activation of caspase-9, -3 and -8, cleavage of poly ADP ribose polymerase (PARP) and Bid in KB cells. Flavokawain B also down-regulate BcI-2 with concomitant increase in Bax level, which resulted in release of cytochrome c. Taken together, the induction of apoptosis by flavokawain B involved in both death receptor and mitochondrial pathway. We also observed that flavokawain B caused the G2/M phase arrest that was mediated through reductions in the levels of cyclin A, cyclin B1, Cdc2 and Cdc25C and increases in p21/WAF1, Wee1 and p53 levels. Moreover, flavokawain B significantly inhibits matrix metalloproteinase-9 and urokinase plasminogen activator expression, whereas tissue inhibitor of matrix metalloproteinase-1 and plasminogen activator inhibitor-1 were increased, which are playing critical role in tumor metastasis. In addition, flavokawain B treatment significantly inhibited in vivo growth of human KB cell-derived tumor xenografts in nude mice, which is evidenced by augmentation of apoptotic DNA fragmentation, as detected by in situ terminal deoxynucleotidyl transferase-meditated dUTP nick end-labeling staining. The induction of cell cycle arrest and apoptosis by flavokawain B may provide a pivotal mechanism for its cancer chemopreventive action. (C) 2012 Elsevier Inc. All rights reserved.
ISSN: 0955-2863
DOI: 10.1016/j.jnutbio.2011.01.002
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