國家衛生研究院 NHRI:Item 3990099045/6636

NHRI > Institute of Biotechnology and Pharmaceutical Research > Shiow-Lin Pan(2009-2013) > Periodical Articles > Item 3990099045/6636

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/6636

Title:	Aciculatin induces p53-dependent apoptosis via MDM2 depletion in human cancer cells in vitro and in vivo
Authors:	Lai, CY;Tsai, AC;Chen, MC;Chang, LH;Sun, HL;Chang, YL;Chen, CC;Teng, CM;Pan, SL
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	Aciculatin, a natural compound extracted from the medicinal herb Chrysopogon aciculatus, shows potent anti-cancer potency. This study is the first to prove that aciculatin induces cell death in human cancer cells and HCT116 mouse xenografts due to G1 arrest and subsequent apoptosis. The primary reason for cell cycle arrest and cell death was p53 accumulation followed by increased p21 level, dephosphorylation of Rb protein, PUMA expression, and induction of apoptotic signals such as cleavage of caspase-9, caspase-3, and PARP. We demonstrated that p53 allele-null (−/−) (p53-KO) HCT116 cells were more resistant to aciculatin than cells with wild-type p53 (+/+). The same result was achieved by knocking down p53 with siRNA in p53 wild-type cells, indicating that p53 plays a crucial role in aciculatin-induced apoptosis. Although DNA damage is the most common event leading to p53 activation, we found only weak evidence of DNA damage after aciculatin treatment. Interestingly, the aciculatin-induced downregulation of MDM2, an important negative regulator of p53, contributed to p53 accumulation. The anti-cancer activity and importance of p53 after aciculatin treatment were also confirmed in the HCT116 xenograft models. Collectively, these results indicate that aciculatin treatment induces cell cycle arrest and apoptosis via inhibition of MDM2 expression, thereby inducing p53 accumulation without significant DNA damage and genome toxicity.
Date:	2012-08-13
Relation:	PLoS ONE. 2012 Aug 13;7(8):Article number e42192.
Link to:	http://dx.doi.org/10.1371/journal.pone.0042192
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1932-6203&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000307500100008
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84865050263
Appears in Collections:	[Shiow-Lin Pan(2009-2013)] Periodical Articles

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