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Flavokawain B Inhibits Growth of Human Squamous Carcinoma Cells: Involvement of Apoptosis and Cell Cycle Dysregulation in Vitro and in Vivo

Flavokawain B Inhibits Growth of Human Squamous Carcinoma Cells: Involvement of Apoptosis and Cell Cycle Dysregulation in Vitro and in Vivo

Elong Lin, Wen-Hsin Lin, Sheng-Yang Wang, Chih-Sheng Chen, Jiuun-Wang Liao, Hsueh-Wei Chang, Ssu-Ching Chen, Kai-Yuan Lin, Lai Wang, Hsin-Ling Yang, You-Cheng Hseu

J Nutr Biochem. 2012 Apr;23(4):368-78.

PMID: 21543203

Abstract:

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 μg/ml; 17.6-70.4 μM) 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 Bcl-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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1775979	Flavokawain B		1775-97-9	Price

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