Cell Reports (Jan 2013)
Gambogic Acid Is a Tissue-Specific Proteasome Inhibitor In Vitro and In Vivo
- Xiaofen Li,
- Shouting Liu,
- Hongbiao Huang,
- Ningning Liu,
- Chong Zhao,
- Siyan Liao,
- Changshan Yang,
- Yurong Liu,
- Canguo Zhao,
- Shujue Li,
- Xiaoyu Lu,
- Chunjiao Liu,
- Lixia Guan,
- Kai Zhao,
- Xiaoqing Shi,
- Wenbin Song,
- Ping Zhou,
- Xiaoxian Dong,
- Haiping Guo,
- Guanmei Wen,
- Change Zhang,
- Lili Jiang,
- Ningfang Ma,
- Bing Li,
- Shunqing Wang,
- Huo Tan,
- Xuejun Wang,
- Q. Ping Dou,
- Jinbao Liu
Affiliations
- Xiaofen Li
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Shouting Liu
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Hongbiao Huang
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Ningning Liu
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Chong Zhao
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Siyan Liao
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Changshan Yang
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Yurong Liu
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Canguo Zhao
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Shujue Li
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Xiaoyu Lu
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Chunjiao Liu
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Lixia Guan
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Kai Zhao
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Xiaoqing Shi
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Wenbin Song
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Ping Zhou
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Xiaoxian Dong
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Haiping Guo
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Guanmei Wen
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Change Zhang
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Lili Jiang
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Ningfang Ma
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Bing Li
- Experiment Medical Research Center, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Shunqing Wang
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Huo Tan
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- Xuejun Wang
- Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, Vermillion, SD 57069, USA
- Q. Ping Dou
- The Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, and Departments of Oncology, Pharmacology and Pathology, School of Medicine, Wayne State University, Detroit, MI 48201-2013, USA
- Jinbao Liu
- Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical College, Guangzhou, Guangdong 510182, China
- DOI
- https://doi.org/10.1016/j.celrep.2012.11.023
- Journal volume & issue
-
Vol. 3,
no. 1
pp. 211 – 222
Abstract
Gambogic acid (GA) is a natural compound derived from Chinese herbs that has been approved by the Chinese Food and Drug Administration for clinical trials in cancer patients; however, its molecular targets have not been thoroughly studied. Here, we report that GA inhibits tumor proteasome activity, with potency comparable to bortezomib but much less toxicity. First, GA acts as a prodrug and only gains proteasome-inhibitory function after being metabolized by intracellular CYP2E1. Second, GA-induced proteasome inhibition is a prerequisite for its cytotoxicity and anticancer effect without off-targets. Finally, because expression of the CYP2E1 gene is very high in tumor tissues but low in many normal tissues, GA could therefore produce tissue-specific proteasome inhibition and tumor-specific toxicity, with clinical significance for designing novel strategies for cancer treatment.
