Antitumor effects of novel compound, guttiferone K, on colon cancer by p21Waf1/Cip1-mediated G0/G1 cell cycle arrest and apoptosis

	Antitumor effects of novel compound, guttiferone K, on colon cancer by p21Waf1/Cip1-mediated G0/G1 cell cycle arrest and apoptosis
	Kan, Winnie Lai Ting 1; Yin, Chun 1; Xu, Hong Xi 2; Xu, Gang3 ; To, Kenneth Kin Wah 4; Cho, Chi Hin 1; Rudd, John Anthony 1; Lin, Ge 1
通讯作者	Lin, G (reprint author), Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Room 505A,5-F Lo Kwee Seong Integrated Biomed Sci, Shatin, Hong Kong, Peoples R China.，xuhongxi88@gmail.com ; linge@cuhk.edu.hk
	2013-02-01
发表期刊	INTERNATIONAL JOURNAL OF CANCER
ISSN	0020-7136
卷号	132 期号:3 页码:707-716
摘要	Low selectivity is one of the major problems of currently used anticancer drugs, therefore, there is a high demand for novel, selective antitumor agents. In this study, the anticancer effects and mechanisms of guttiferone K (GUTK), a novel polyprenylated acylphloroglucinol derivative isolated from Garcinia cowa Roxb., were examined for its development as a novel drug targeting colon cancer. GUTK concentration- and time-dependently reduced the viability of human colon cancer HT-29 cells (IC50 value 5.39 +/- 0.22 mu M) without affecting the viability of normal human colon epithelial CCD 841 CoN cells and induced G0/G1 cell cycle arrest in HT-29 cells by down-regulating cyclins D1, D3 and cyclin-dependent kinases 4 and 6, while selectively restoring p21Waf1/Cip1 and p27Kip1 to levels comparable to those observed in normal colon cells, without affecting their levels in normal cells. GUTK (10.0 mu M) induced cleavage of PARP, caspases-3, -8 and -9 and chromatin condensation to stimulate caspase-3-mediated apoptosis. The addition of a JNK inhibitor, SP600125, partially reversed GUTK-induced caspase-3 activity, indicating the possible involvement of JNK in GUTK-induced apoptosis. Furthermore, GUTK (10 mg/kg, i.p.) significantly decreased the tumor volume in a syngeneic colon tumor model when used alone or in combination with 5-fluorouracil without toxicity to the mice. Immunohistochemical staining of the tumor sections revealed a mechanism involving an increase in cleaved caspase-3 and a decrease in cell proliferation marker Ki-67. Our results support GUTK as a promising novel, potent and selective antitumor drug candidate for colon cancer.
关键词	Guttiferone k Anti-tumor Colon Cancer Apoptosis Cell Cycle
学科领域	Oncology
收录类别	SCI
语种	英语
WOS记录号	WOS:000311620100028
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/16218
专题	植物化学与西部植物资源持续利用国家重点实验室
作者单位	1.Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Shatin, Hong Kong, Peoples R China 2.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai, Peoples R China 3.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources W China, Kunming, Peoples R China 4.Chinese Univ Hong Kong, Sch Pharm, Fac Med, Shatin, Hong Kong, Peoples R China
推荐引用方式 GB/T 7714	Kan, Winnie Lai Ting,Yin, Chun,Xu, Hong Xi,et al. Antitumor effects of novel compound, guttiferone K, on colon cancer by p21Waf1/Cip1-mediated G0/G1 cell cycle arrest and apoptosis[J]. INTERNATIONAL JOURNAL OF CANCER,2013,132(3):707-716.
APA	Kan, Winnie Lai Ting.,Yin, Chun.,Xu, Hong Xi.,Xu, Gang.,To, Kenneth Kin Wah.,...&Lin, Ge.(2013).Antitumor effects of novel compound, guttiferone K, on colon cancer by p21Waf1/Cip1-mediated G0/G1 cell cycle arrest and apoptosis.INTERNATIONAL JOURNAL OF CANCER,132(3),707-716.
MLA	Kan, Winnie Lai Ting,et al."Antitumor effects of novel compound, guttiferone K, on colon cancer by p21Waf1/Cip1-mediated G0/G1 cell cycle arrest and apoptosis".INTERNATIONAL JOURNAL OF CANCER 132.3(2013):707-716.

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