4.3 Article

Blockade of γ-Glutamylcyclotransferase Enhances Docetaxel Growth Inhibition of Prostate Cancer Cells

Journal

ANTICANCER RESEARCH
Volume 39, Issue 9, Pages 4811-4816

Publisher

INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.13666

Keywords

gamma-glutamylcyclotransferase; prostate cancer cells; senescence; docetaxel; pro-GA

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Funding

  1. JSPS [15K20084, 16K08722, 18K09192]
  2. MEXT Program for the Strategic Research Foundation at Private Universities 2015-2019
  3. Takeda Science Foundation
  4. KPU Fund for the Promotion of Collaborative Research
  5. PMAC
  6. Grants-in-Aid for Scientific Research [18K09192, 16K08722, 15K20084] Funding Source: KAKEN

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Background/Aim: gamma-Glutamylcyclotransferase (GGCT) is highly expressed in many forms of cancer, and is a promising therapeutic target. The present study investigated whether inhibition of GGCT enhanced the antiproliferative effects of the drug docetaxel in prostate cancer cells. Materials and Methods: Immunohistochemistry and western blot analysis were conducted to measure GGCT expression in prostate cancer tissue samples and cell lines. GGCT was inhibited using RNAi and a novel enzymatic inhibitor, pro-GA, and cell proliferation was evaluated with single and combination treatments of GGCT inhibitors and docetaxel. Results: GGCT was highly expressed in cultured prostate cancer cells and patient samples. GGCT inhibition alone inhibited prostate cancer cell line proliferation and induced cellular senescence. GGCT inhibition in combination with apoptosis-inducing docetaxel had more potent antiproliferative effects than either drug used alone. Conclusion: GGCT inhibition may potentiate anticancer drug efficacy.

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