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 WenChange Zhang, Lili Jiang, Ningfang Ma, Bing Li, Shunqing Wang, Huo Tan, Xuejun Wang, Q. Ping Dou, Jinbao Liu

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)211-222
Number of pages12
JournalCell Reports
Volume3
Issue number1
DOIs
StatePublished - Jan 31 2013

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Proteasome Inhibitors
Proteasome Endopeptidase Complex
Tissue
Tumors
Cytochrome P-450 CYP2E1
Neoplasms
Toxicity
Oncology
Prodrugs
United States Food and Drug Administration
Cytotoxicity
Genes
gambogic acid
In Vitro Techniques
Clinical Trials
Gene Expression

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Li, X., Liu, S., Huang, H., Liu, N., Zhao, C., Liao, S., ... Liu, J. (2013). Gambogic Acid Is a Tissue-Specific Proteasome Inhibitor In Vitro and In Vivo. Cell Reports, 3(1), 211-222. https://doi.org/10.1016/j.celrep.2012.11.023

Gambogic Acid Is a Tissue-Specific Proteasome Inhibitor In Vitro and In Vivo. / Li, Xiaofen; Liu, Shouting; Huang, Hongbiao; Liu, Ningning; Zhao, Chong; Liao, Siyan; Yang, Changshan; Liu, Yurong; Zhao, Canguo; Li, Shujue; Lu, Xiaoyu; Liu, Chunjiao; Guan, Lixia; Zhao, Kai; Shi, Xiaoqing; Song, Wenbin; Zhou, Ping; Dong, Xiaoxian; Guo, Haiping; Wen, Guanmei; Zhang, Change; Jiang, Lili; Ma, Ningfang; Li, Bing; Wang, Shunqing; Tan, Huo; Wang, Xuejun; Dou, Q. Ping; Liu, Jinbao.

In: Cell Reports, Vol. 3, No. 1, 31.01.2013, p. 211-222.

Research output: Contribution to journalArticle

Li, X, Liu, S, Huang, H, Liu, N, Zhao, C, Liao, S, Yang, C, Liu, Y, Zhao, C, Li, S, Lu, X, Liu, C, Guan, L, Zhao, K, Shi, X, Song, W, Zhou, P, Dong, X, Guo, H, Wen, G, Zhang, C, Jiang, L, Ma, N, Li, B, Wang, S, Tan, H, Wang, X, Dou, QP & Liu, J 2013, 'Gambogic Acid Is a Tissue-Specific Proteasome Inhibitor In Vitro and In Vivo', Cell Reports, vol. 3, no. 1, pp. 211-222. https://doi.org/10.1016/j.celrep.2012.11.023
Li, Xiaofen ; Liu, Shouting ; Huang, Hongbiao ; Liu, Ningning ; Zhao, Chong ; Liao, Siyan ; Yang, Changshan ; Liu, Yurong ; Zhao, Canguo ; Li, Shujue ; Lu, Xiaoyu ; Liu, Chunjiao ; Guan, Lixia ; Zhao, Kai ; Shi, Xiaoqing ; Song, Wenbin ; Zhou, Ping ; Dong, Xiaoxian ; Guo, Haiping ; Wen, Guanmei ; Zhang, Change ; Jiang, Lili ; Ma, Ningfang ; Li, Bing ; Wang, Shunqing ; Tan, Huo ; Wang, Xuejun ; Dou, Q. Ping ; Liu, Jinbao. / Gambogic Acid Is a Tissue-Specific Proteasome Inhibitor In Vitro and In Vivo. In: Cell Reports. 2013 ; Vol. 3, No. 1. pp. 211-222.
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AU - Dong, Xiaoxian

AU - Guo, Haiping

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AU - Jiang, Lili

AU - Ma, Ningfang

AU - Li, Bing

AU - Wang, Shunqing

AU - Tan, Huo

AU - Wang, Xuejun

AU - Dou, Q. Ping

AU - Liu, Jinbao

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