Flavokawain B inhibits growth of human squamous carcinoma cells: Involvement of apoptosis and cell cycle dysregulation in vitro and in vivo

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Title:	Flavokawain B inhibits growth of human squamous carcinoma cells: Involvement of apoptosis and cell cycle dysregulation in vitro and in vivo
Authors:	陳師慶;Lin, Elong;Lin, Wen-Hsin;Wang, Sheng-Yang;Chen, Chih-Sheng;Liao, Jiuun-Wang;Chang, Hsueh-Wei;Chen, Ssu-Ching;Lin, Kai-Yuan;Wang, Lai;Yang, Hsin-Ling;Hseu, You-Cheng
Contributors:	生醫理工學院生命科學系
Keywords:	adenosine diphosphate;Animals;Apoptosis;Apoptosis - drug effects;bcl-2-Associated X Protein;bcl-2-Associated X Protein - genetics;bcl-2-Associated X Protein - metabolism;Biological and medical sciences;Carcinoma;Carcinoma, Squamous Cell;Carcinoma, Squamous Cell - pathology;Caspase 3;Caspase 3 - genetics;Caspase 3 - metabolism;Caspase 8;Caspase 8 - genetics;Caspase 8 - metabolism;Caspase 9;Caspase 9 - genetics;Caspase 9 - metabolism;Cell cycle;Cell cycle arrest;Cell Cycle Checkpoints;Cell Cycle Checkpoints - drug effects;Cell Division;Cell Division - drug effects;Cell Line, Tumor;Cell Proliferation;Cell Proliferation - drug effects;cell viability;Chalcone;Cyclin B1;Cyclin-dependent kinase inhibitor p21;Cytochromes c;Cytochromes c - genetics;Cytochromes c - metabolism;death;death receptors;DNA fragmentation;DNA Fragmentation - drug effects;double prime KB cells;Down-Regulation;drug effects;Feeding. Feeding behavior;Female;Flavokawain B;Flavonoids;Flavonoids - pharmacology;Fundamental and applied biological sciences. Psychology;gelatinase A;genetics;genomics;Humans;interstitial collagenase;KB cells;Lymphocytes B;Matrix Metalloproteinase 1;Matrix Metalloproteinase 1 - genetics;Matrix Metalloproteinase 1 - metabolism;Matrix Metalloproteinase 9;Matrix Metalloproteinase 9 - genetics;Matrix Metalloproteinase 9 - metabolism;metabolism;metastasis;Mice;Mice, Inbred BALB C;Mitochondria;Mitochondria - drug effects;Mitochondria - metabolism;p53 protein;pathology;pharmacology;plasminogen;Poly (ADP-Ribose) Polymerase-1;Poly(ADP-ribose) Polymerases;Poly(ADP-ribose) Polymerases - genetics;Poly(ADP-ribose) Polymerases - metabolism;Rhizomes;Ribose;Tumors;u-Plasminogen activator;Urokinase-Type Plasminogen Activator;Urokinase-Type Plasminogen Activator - genetics;Urokinase-Type Plasminogen Activator - metabolism;Vertebrates: anatomy and physiology, studies on body, several organs or systems;Xenografts
Date:	2012-04-01
Issue Date:	2026-04-23 11:12:45 (UTC+8)
Publisher:	Elsevier Inc.;New York, NY: Elsevier Inc
Abstract:	摘要： 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. 其他題名： J Nutr Biochem 出版者： New York, NY: Elsevier Inc 出版日期： 2012-04-01 出處： The Journal of nutritional biochemistry, 2012-04, Vol.23 (4), p.368-378 版權： 2012 Elsevier Inc. 版權： 2015 INIST-CNRS 版權： Copyright Â© 2012 Elsevier Inc. All rights reserved. 識別號： ISSN: 0955-2863 識別號： ISSN: 1873-4847 識別號： EISSN: 1873-4847 識別號： DOI: 10.1016/j.jnutbio.2011.01.002 識別號： PMID: 21543203
Appears in Collections:	[Department of Life Science] journal & Dissertation

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