Quantitative proteomics reveals molecular mechanism of gamabufotalin and its potential inhibition on Hsp90 in lung cancer.
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| Abstract |
Gamabufotalin (CS-6) is a major bufadienolide of Chansu, which shows desirable metabolic stability and less adverse effect in cancer therapy. CS-6 treatment inhibited the proliferation of NSCLC in a nanomolar range. And CS-6 could induce G2/M cell cycle arrest and apoptosis in A549 cells. However, its molecular mechanism in antitumor activity remains poorly understood. We employed a quantitative proteomics approach to identify the potential cellular targets of CS-6, and found 38 possible target-related proteins. Among them, 31 proteins were closely related in the protein-protein interaction network. One of the regulatory nodes in key pathways was occupied by Hsp90. Molecular docking revealed that CS-6 interacted with the ATP-binding sites of Hsp90. In addition, CS-6 inhibited the chaperone function of Hsp90 and reduced expression of Hsp90-dependent client proteins. Moreover, CS-6 markedly down-regulated the protein level of Hsp90 in tumor tissues of the xenograft mice. Taken together, our results suggest that CS-6 might be a novel inhibitor of Hsp90, and the possible network associated with CS-6 target-related proteins was constructed, which provided experimental evidence for the preclinical value of using CS-6 as an effective antitumor agent in treatment of NSCLC.
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| Authors | Liyuan Zhang, Zhenlong Yu, Yan Wang, Xiaobo Wang, Lianru Zhang, Chao Wang, Qingxi Yue, Xun Wang, Sa Deng, Xiaokui Huo, Xiangge Tian, Shanshan Huang, Baojing Zhang, Xiaochi Ma |
| Journal | Oncotarget (Oncotarget) Vol. 7 Issue 47 Pg. 76551-76564 (Nov 22 2016) ISSN: 1949-2553 [Electronic] United States |
| PMID | 27384878 (Publication Type: Journal Article) |
| Chemical References |
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