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Anti-tumor activity of the TRPM8 inhibitor BCTC in prostate cancer DU145 cells

  • Authors:
    • Tao Liu
    • Zhihai Fang
    • Gang Wang
    • Mingjun Shi
    • Xiao Wang
    • Kun Jiang
    • Zhonghua Yang
    • Rui Cao
    • Huangheng Tao
    • Xinghuan Wang
    • Jiajie Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Jingzhou Central Hospital, Jingzhou, Hubei 434020, P.R. China, Department of Urology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China, Key Laboratory for Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 182-188
    |
    Published online on: November 2, 2015
       https://doi.org/10.3892/ol.2015.3854
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Abstract

The present study investigated the anti‑tumor activity of N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carbox-amide (BCTC), a potent and specific inhibitor of transient receptor potential cation channel subfamily M member 8 (TRPM8) in prostate cancer (PCa) DU145 cells. TRPM8 expression in DU145 and normal prostate PNT1A cells was detected by reverse transcription polymerase chain reaction and western blot analysis. The effect of BCTC on DU145 cells was analyzed by flow cytometry analysis, and MTT, scratch motility and Transwell invasion assays. The molecular mechanism through which BCTC acts was investigated by western blot analysis. TRPM8 expression was increased in DU145 cells compared with PNT1A cells at the mRNA and protein levels. The present study provided evidence that inhibition of TRPM8 by BCTC reduced the viability of DU145 cells, but not PNT1A cells. In addition, BCTC inhibited cell cycle progression, migration and invasion in DU145 cells. Cell cycle‑associated proteins, including phosphorylated protein kinase B, cyclin D1, cyclin dependent kinase (CDK) 2 and CDK6 were downregulated by BCTC, while phosphorylated glycogen synthase kinase 3β was upregulated. However, investigations in the present study revealed that BCTC failed to trigger apoptosis in DU145 cells. In addition, in BCTC‑treated DU145 cells, phosphorylated extracellular signal‑regulated kinase 1/2 was downregulated substantially while phosphorylated p38 (p‑p38) and phosphorylated c‑Jun N‑terminal kinases (p‑JNK) were upregulated. The anti‑proliferative activity of BCTC on DU145 cells was attenuated by p38 and JNK‑specific inhibitors, suggesting that MAPK pathways are involved. Overall, the TRPM8 specific antagonist BCTC demonstrated excellent anti‑tumor activity in PCa DU145 cells, and therefore has the potential to become a targeted therapeutic strategy against PCa.
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Copy and paste a formatted citation
Spandidos Publications style
Liu T, Fang Z, Wang G, Shi M, Wang X, Jiang K, Yang Z, Cao R, Tao H, Wang X, Wang X, et al: Anti-tumor activity of the TRPM8 inhibitor BCTC in prostate cancer DU145 cells. Oncol Lett 11: 182-188, 2016.
APA
Liu, T., Fang, Z., Wang, G., Shi, M., Wang, X., Jiang, K. ... Zhou, J. (2016). Anti-tumor activity of the TRPM8 inhibitor BCTC in prostate cancer DU145 cells. Oncology Letters, 11, 182-188. https://doi.org/10.3892/ol.2015.3854
MLA
Liu, T., Fang, Z., Wang, G., Shi, M., Wang, X., Jiang, K., Yang, Z., Cao, R., Tao, H., Wang, X., Zhou, J."Anti-tumor activity of the TRPM8 inhibitor BCTC in prostate cancer DU145 cells". Oncology Letters 11.1 (2016): 182-188.
Chicago
Liu, T., Fang, Z., Wang, G., Shi, M., Wang, X., Jiang, K., Yang, Z., Cao, R., Tao, H., Wang, X., Zhou, J."Anti-tumor activity of the TRPM8 inhibitor BCTC in prostate cancer DU145 cells". Oncology Letters 11, no. 1 (2016): 182-188. https://doi.org/10.3892/ol.2015.3854
Copy and paste a formatted citation
x
Spandidos Publications style
Liu T, Fang Z, Wang G, Shi M, Wang X, Jiang K, Yang Z, Cao R, Tao H, Wang X, Wang X, et al: Anti-tumor activity of the TRPM8 inhibitor BCTC in prostate cancer DU145 cells. Oncol Lett 11: 182-188, 2016.
APA
Liu, T., Fang, Z., Wang, G., Shi, M., Wang, X., Jiang, K. ... Zhou, J. (2016). Anti-tumor activity of the TRPM8 inhibitor BCTC in prostate cancer DU145 cells. Oncology Letters, 11, 182-188. https://doi.org/10.3892/ol.2015.3854
MLA
Liu, T., Fang, Z., Wang, G., Shi, M., Wang, X., Jiang, K., Yang, Z., Cao, R., Tao, H., Wang, X., Zhou, J."Anti-tumor activity of the TRPM8 inhibitor BCTC in prostate cancer DU145 cells". Oncology Letters 11.1 (2016): 182-188.
Chicago
Liu, T., Fang, Z., Wang, G., Shi, M., Wang, X., Jiang, K., Yang, Z., Cao, R., Tao, H., Wang, X., Zhou, J."Anti-tumor activity of the TRPM8 inhibitor BCTC in prostate cancer DU145 cells". Oncology Letters 11, no. 1 (2016): 182-188. https://doi.org/10.3892/ol.2015.3854
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