Gambogic acid enhances proteasome inhibitor-induced anticancer activity

被引：55

作者：

Huang, Hongbiao ^{[1
]}

Chen, Di ^{[2
,3
,4
,5
]}

Li, Shujue ^{[1
,6
]}

Li, Xiaofen ^{[1
]}

Liu, Ningning ^{[1
]}

Lu, Xiaoyu ^{[1
]}

Liu, Shouting ^{[1
]}

Zhao, Kai ^{[1
]}

Zhao, Canguo ^{[1
]}

Guo, Haiping ^{[1
]}

Yang, Changshan ^{[1
]}

Zhou, Ping ^{[1
]}

Dong, Xiaoxian ^{[1
]}

Zhang, Change ^{[1
]}

Guanmei ^{[1
]}

Dou, Q. Ping ^{[1
,2
,3
,4
,5
]}

Liu, Jinbao ^{[1
]}

机构：

[1] Guangzhou Med Univ, Prot Modificat & Degradat Lab, Dept Pathophysiol, Guangzhou 510182, Guangdong, Peoples R China

[2] Wayne State Univ, Sch Med, Dev Therapeut Program, Barbara Ann Karmanos Canc Inst, Detroit, MI 48201 USA

[3] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI 48201 USA

[4] Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA

[5] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA

[6] Guangzhou Med Univ, Dept Urol, Minimally Invas Surg Ctr, Affiliated Hosp 1, Guangzhou 510230, Guangdong, Peoples R China

来源：

CANCER LETTERS | 2011年 / 301卷 / 02期

基金：

国家高技术研究发展计划(863计划);

关键词：

Gambogic acid; Proteasome inhibitors; Antitumor activity; Synergistic effect; FACTOR-KAPPA-B; HUMAN BREAST-CANCER; INDUCED APOPTOSIS; MULTIPLE-MYELOMA; DOWN-REGULATION; IN-VITRO; DOXORUBICIN; INDUCTION; CURCUMIN; GROWTH;

D O I：

10.1016/j.canlet.2010.12.015

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

引用

页码：221 / 228

页数：8

共 43 条

[1]

Adams J, 1999, CANCER RES, V59, P2615

[2] The proteasome: A suitable antineoplastic target [J].