Gambogic acid enhances proteasome inhibitor-induced anticancer activity.

Abstract	Proteasome inhibition has emerged as a novel approach to anticancer therapy. Numerous natural compounds, such as gambogic acid, have been tested in vitro and in vivo as anticancer agents for cancer prevention and therapy. However, whether gambogic acid has chemosensitizing properties when combined with proteasome inhibitors in the treatment of malignant cells is still unknown. In an effort to investigate this effect, human leukemia K562 cells, mouse hepatocarcinoma H22 cells and H22 cell allografts were treated with gambogic acid, a proteasome inhibitor (MG132 or MG262) or the combination of both, followed by measurement of cellular viability, apoptosis induction and tumor growth inhibition. We report, for the first time, that: (i) the combination of natural product gambogic acid and the proteasome inhibitor MG132 or MG262 results in a synergistic inhibitory effect on growth of malignant cells and tumors in allograft animal models and (ii) there was no apparent systemic toxicity observed in the animals treated with the combination. Therefore, the findings presented in this study demonstrate that natural product gambogic acid is a valuable candidate to be used in combination with proteasome inhibitors, thus representing a compelling anticancer strategy.
Authors	Hongbiao Huang, Di Chen, Shujue Li, Xiaofen Li, Ningning Liu, Xiaoyu Lu, Shouting Liu, Kai Zhao, Canguo Zhao, Haiping Guo, Changshan Yang, Ping Zhou, Xiaoxian Dong, Change Zhang, Guanmei, Q Ping Dou, Jinbao Liu
Journal	Cancer letters (Cancer Lett) Vol. 301 Issue 2 Pg. 221-8 (Feb 28 2011) ISSN: 1872-7980 [Electronic] Ireland
PMID	21216092 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright	Copyright Â© 2010 Elsevier Ireland Ltd. All rights reserved.
Chemical References	Amino Acid Chloromethyl Ketones Boronic Acids Caspase Inhibitors Cysteine Proteinase Inhibitors Leupeptins MG 262 Proteasome Inhibitors Protein Synthesis Inhibitors Xanthones benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone gambogic acid Cycloheximide Caspases Proteasome Endopeptidase Complex benzyloxycarbonylleucyl-leucyl-leucine aldehyde
Topics	Amino Acid Chloromethyl Ketones (pharmacology) Animals Antineoplastic Combined Chemotherapy Protocols (therapeutic use) Apoptosis (drug effects) Blotting, Western Boronic Acids (administration & dosage, pharmacology) Caspase Inhibitors Caspases (metabolism) Cell Line, Tumor Cell Survival (drug effects) Cycloheximide (pharmacology) Cysteine Proteinase Inhibitors (administration & dosage, pharmacology) Drug Synergism Humans K562 Cells Leupeptins (administration & dosage, pharmacology) Male Mice Neoplasms, Experimental (drug therapy, metabolism, pathology) Proteasome Endopeptidase Complex (metabolism) Proteasome Inhibitors Protein Synthesis Inhibitors (pharmacology) Signal Transduction (drug effects) Transplantation, Homologous Tumor Burden (drug effects) Xanthones (administration & dosage, pharmacology)

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