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.
journal_name
Cell Repjournal_title
Cell reportsauthors
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 Jdoi
10.1016/j.celrep.2012.11.023subject
Has Abstractpub_date
2013-01-31 00:00:00pages
211-22issue
1issn
2211-1247pii
S2211-1247(12)00420-2journal_volume
3pub_type
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