Gambogic acid inhibits growth, induces apoptosis, and overcomes drug resistance in human colorectal cancer cells

被引:51
作者
Wen, Chuangyu [1 ,2 ,3 ,4 ,5 ]
Huang, Lanlan [1 ,2 ,3 ,4 ,5 ]
Chen, Junxiong [1 ,2 ,3 ,4 ,5 ]
Lin, Mengmeng [1 ,2 ,3 ,4 ,5 ]
Li, Wen [6 ]
Lu, Biyan [7 ]
Rutnam, Zina Jeyapalan [8 ]
Iwamoto, Aikichi [9 ]
Wang, Zhongyang [1 ,2 ]
Yang, Xiangling [1 ,2 ,3 ,4 ,5 ]
Liu, Huanliang [1 ,2 ,3 ,4 ,5 ]
机构
[1] Sun Yat Sen Univ, Guangdong Inst Gastroenterol, Guangzhou 510655, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Affiliated Hosp 6, Guangzhou 510655, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Guangdong Prov Key Lab Colorectal & Pelv Floor Di, Guangzhou 510655, Guangdong, Peoples R China
[4] Sun Yat Sen Univ, Minist Educ, Inst Human Virol, Guangzhou 510080, Guangdong, Peoples R China
[5] Sun Yat Sen Univ, Minist Educ, Key Lab Trop Dis Control, Guangzhou 510080, Guangdong, Peoples R China
[6] Guangzhou Med Univ, Guangdong Prov Key Lab Allergy & Immunol, Guangzhou 510260, Guangdong, Peoples R China
[7] Dongguan Hlth Sch, Dongguan 523186, Guangdong, Peoples R China
[8] Univ Washington, Ctr Translat Med Womens Hlth, Tumor Vaccine Grp, Seattle, WA 98195 USA
[9] Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Tokyo 1088639, Japan
关键词
gambogic acid; colorectal cancer; 5-FU resistance; apoptosis; JNK signaling pathway; C-JUN; TRANSCRIPTION FACTOR; P-GLYCOPROTEIN; BREAST-CANCER; CYCLE ARREST; IN-VITRO; KINASE; MITOCHONDRIA; CHEMOTHERAPY; BCL-2;
D O I
10.3892/ijo.2015.3166
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The emergence of chemoresistance is a major limitation of colorectal cancer (CRC) therapies and novel biologically based therapies are urgently needed. Natural products represent a novel potential anticancer therapy. Gambogic acid (GA), a small molecule derived from Garcinia hanburyi Hook. f., has been demonstrated to be highly cytotoxic to several types of cancer cells and have low toxicity to the hematopoietic system. However, the potential role of GA in colorectal cancer and its ability to overcome the chemotherapeutic resistance in CRC cells have not been well studied. In the present study, we showed that GA directly inhibited proliferation and induced apoptosis in both 5-fluorouracil (5-FU) sensitive and 5-FU resistant colorectal cancer cells; induced apoptosis via activating JNK signaling pathway. The data, therefore, suggested an alternative strategy to overcome 5-FU resistance in CRC and that GA could be a promising medicinal compound for colorectal cancer therapy.
引用
收藏
页码:1663 / 1671
页数:9
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