CLC604 preferentially inhibits the growth of HER2-overexpressing cancer cells and sensitizes these cells to the inhibitory effect of Taxol in vitro and in vivo

  • Authors:
    • Jang-Chang Lee
    • Li-Chen Chou
    • Jin-Chemg Lien
    • Jia-Chiun Wu
    • Chi-Hung Huang
    • Chao-Ho Chung
    • Fang-Yu Lee
    • Li-Jiau Huang
    • Sheng-Chu Kuo
    • Tzong-Der Way
  • View Affiliations

  • Published online on: July 23, 2013     https://doi.org/10.3892/or.2013.2634
  • Pages: 1762-1772
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Abstract

HER2 has become a solicitous therapeutic target in metastatic and clinical drug-resistant cancer. Here, we evaluated whether or not 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) and its furopyrazole and thienopyrazole analogues repress the expression of the HER2 protein. Among the test compounds, (1-benzyl-3-(p-hydroxymethylphenyl)-5-methylfuro[3,2-c]pyrazol) (CLC604), an isosteric analogue of YC-1, significantly suppressed the expression of HER2, and preferentially inhibited cell proliferation and induced apoptosis in HER2-overexpressing cancer cells. Our results revealed that CLC604 reduced HER2 expression through a post-transcriptional mechanism and involvement of proteasomal activity. CLC604 disrupted the association of 90-kDa heat shock protein (Hsp90) with HER2 resulting from the inhibition of Hsp90 ATPase activity. Moreover, we found that CLC604 significantly enhanced the antitumor efficacy of clinical drugs against HER2-overexpressing tumors and efficiently reduced HER2-induced drug resistance in vitro and in vivo. These findings suggest that CLC604 should be developed further as a novel antitumor drug candidate for the treatment of drug-resistant cancer.
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October 2013
Volume 30 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Lee J, Chou L, Lien J, Wu J, Huang C, Chung C, Lee F, Huang L, Kuo S, Way T, Way T, et al: CLC604 preferentially inhibits the growth of HER2-overexpressing cancer cells and sensitizes these cells to the inhibitory effect of Taxol in vitro and in vivo. Oncol Rep 30: 1762-1772, 2013
APA
Lee, J., Chou, L., Lien, J., Wu, J., Huang, C., Chung, C. ... Way, T. (2013). CLC604 preferentially inhibits the growth of HER2-overexpressing cancer cells and sensitizes these cells to the inhibitory effect of Taxol in vitro and in vivo. Oncology Reports, 30, 1762-1772. https://doi.org/10.3892/or.2013.2634
MLA
Lee, J., Chou, L., Lien, J., Wu, J., Huang, C., Chung, C., Lee, F., Huang, L., Kuo, S., Way, T."CLC604 preferentially inhibits the growth of HER2-overexpressing cancer cells and sensitizes these cells to the inhibitory effect of Taxol in vitro and in vivo". Oncology Reports 30.4 (2013): 1762-1772.
Chicago
Lee, J., Chou, L., Lien, J., Wu, J., Huang, C., Chung, C., Lee, F., Huang, L., Kuo, S., Way, T."CLC604 preferentially inhibits the growth of HER2-overexpressing cancer cells and sensitizes these cells to the inhibitory effect of Taxol in vitro and in vivo". Oncology Reports 30, no. 4 (2013): 1762-1772. https://doi.org/10.3892/or.2013.2634