Canguo Zhao

Publications (5)17.15 Total impact

• Article: 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, [......], Guanmei Wen, Change Zhang, Lili Jiang, Ningfang Ma, Bing Li, Shunqing Wang, Huo Tan, Xuejun Wang, Q Ping Dou, Jinbao Liu
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  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.
  Cell reports. 12/2012;
• Article: Gambogic acid enhances proteasome inhibitor-induced anticancer activity.

  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
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  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.
  Cancer letters 02/2011; 301(2):221-8. · 4.86 Impact Factor
• Source

  Available from: Xiaoqin Yang

  Article: Expression-based in silico screening of candidate therapeutic compounds for lung adenocarcinoma.

  Guiping Wang, Yun Ye, Xiaoqin Yang, Hongying Liao, Canguo Zhao, Shuang Liang
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  ABSTRACT: Lung adenocarcinom (AC) is the most common form of lung cancer. Currently, the number of medical options to deal with lung cancer is very limited. In this study, we aimed to investigate potential therapeutic compounds for lung adenocarcinoma based on integrative analysis. The candidate therapeutic compounds were identified in a two-step process. First, a meta-analysis of two published microarray data was conducted to obtain a list of 343 differentially expressed genes specific to lung AC. In the next step, expression profiles of these genes were used to query the Connectivity-Map (C-MAP) database to identify a list of compounds whose treatment reverse expression direction in various cancer cells. Several compounds in the categories of HSP90 inhibitor, HDAC inhibitor, PPAR agonist, PI3K inhibitor, passed our screening to be the leading candidates. On top of the list, three HSP90 inhibitors, i.e. 17-AAG (also known as tanespimycin), monorden, and alvespimycin, showed significant negative enrichment scores. Cytotoxicity as well as effects on cell cycle regulation and apoptosis were evaluated experimentally in lung adenocarcinoma cell line (A549 or GLC-82) with or without treatment with 17-AAG. In vitro study demonstrated that 17-AAG alone or in combination with cisplatin (DDP) can significantly inhibit lung adenocarcinoma cell growth by inducing cell cycle arrest and apoptosis. We have used an in silico screening to identify compounds for treating lung cancer. One such compound 17-AAG demonstrated its anti-lung AC activity by inhibiting cell growth and promoting apoptosis and cell cycle arrest.
  PLoS ONE 01/2011; 6(1):e14573. · 4.09 Impact Factor
• Article: Sanggenon C decreases tumor cell viability associated with proteasome inhibition.

  Hongbiao Huang, Ningning Liu, Kai Zhao, Chenchen Zhu, Xiaoyu Lu, Shujue Li, Wen Lian, Ping Zhou, Xiaoxian Dong, Canguo Zhao, [......], Change Zhang, Changshan Yang, Guanmei Wen, Li Lu, Xiaofen Li, Lixia Guan, Chunjiao Liu, Xuejun Wang, Qing Ping Dou, Jinbao Liu
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  ABSTRACT: Several flavonoids have been reported to be proteasome inhibitors, but whether prenylated flavonoids are able to inhibit proteasome function remains unknown. We report for the first time that Sanggenon C, a natural prenylated flavonoid, inhibits tumor cellular proteasomal activity and cell viability. We found that (1) Sanggenon C inhibited tumor cell viability and induced cell cycle arrest at G0/G1 phase; (2) Sanggenon C inhibited the chymotrypsin-like activity of purified human 20S proteasome and 26S proteasome in H22 cell lysate, and Sanggenon C was able to dose-dependently accumulate ubiquitinated proteins and proteasome substrate protein p27; (3) Sanggenon C-induced proteasome inhibition occurred prior to cell death in murine H22 and P388 cell lines; (4) Sanggenon C induced death of human K562 cancer cells and primary cells isolated from leukemic patients. We conclude that Sanggenon C inhibits tumor cell viability via induction of cell cycle arrest and cell death, which is associated with its ability to inhibit the proteasome function and that proteasome inhibition by Sanggenon C at least partially contributes to the observed tumor cell growth-inhibitory activity.
  Frontiers in bioscience (Elite edition) 01/2011; 3:1315-25.
• Article: Physiological levels of ATP negatively regulate proteasome function.

  Hongbiao Huang, Xiaoyan Zhang, Shujue Li, Ningning Liu, Wen Lian, Emily McDowell, Ping Zhou, Canguo Zhao, Haiping Guo, Change Zhang, Changshan Yang, Guangmei Wen, Xiaoxian Dong, Li Lu, Ningfang Ma, Weihua Dong, Q Ping Dou, Xuejun Wang, Jinbao Liu
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  ABSTRACT: Intracellular protein degradation by the ubiquitin-proteasome system is ATP dependent, and the optimal ATP concentration to activate proteasome function in vitro is ∼100 μM. Intracellular ATP levels are generally in the low millimolar range, but ATP at a level within this range was shown to inhibit proteasome peptidase activities in vitro. Here, we report new evidence that supports a hypothesis that intracellular ATP at the physiological levels bidirectionally regulates 26S proteasome proteolytic function in the cell. First, we confirmed that ATP exerted bidirectional regulation on the 26S proteasome in vitro, with the optimal ATP concentration (between 50 and 100 μM) stimulating proteasome chymotrypsin-like activities. Second, we found that manipulating intracellular ATP levels also led to bidirectional changes in the levels of proteasome-specific protein substrates in cultured cells. Finally, measures to increase intracellular ATP enhanced, while decreasing intracellular ATP attenuated the ability of proteasome inhibition to induce cell death. These data strongly suggest that endogenous ATP within the physiological concentration range can exert a negative impact on proteasome activities, allowing the cell to rapidly upregulate proteasome activity on ATP reduction under stress conditions.
  Cell Research 12/2010; 20(12):1372-85. · 8.19 Impact Factor