Antitumor effects of novel compound, guttiferone K, on colon cancer by p21Waf1/Cip1-mediated G0/G1 cell cycle arrest and apoptosis
Kan, Winnie Lai Ting1; Yin, Chun1; Xu, Hong Xi2; Xu, Gang3; To, Kenneth Kin Wah4; Cho, Chi Hin1; Rudd, John Anthony1; Lin, Ge1
2013-02-01
发表期刊INTERNATIONAL JOURNAL OF CANCER
ISSN0020-7136
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
资助信息CUHK Direct Grant from The Chinese University of Hong Kong [2041445]; NSF fund from the National Natural Science Foundation of China [81173485]
学科领域Oncology
收录类别SCI
语种英语
WOS研究方向Oncology
WOS类目Oncology
WOS记录号WOS:000311620100028
引用统计
被引频次:28[WOS]   [WOS记录]     [WOS相关记录]
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
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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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