Docetaxel induces Bcl-2- and pro-apoptotic caspase-independent death of human prostate cancer DU145 cells
| Autor: | Hiroki Tamaki, Mamoru Harada, Takeharu Ogura, Yoshiyuki Tanaka |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology Male Cancer Research medicine.medical_specialty caspase Mice Nude Antineoplastic Agents Apoptosis Docetaxel urologic and male genital diseases Transfection 03 medical and health sciences Prostate cancer Mice 0302 clinical medicine DU145 Cancer stem cell Internal medicine Cell Line Tumor LNCaP medicine Animals Humans Bcl-2 neoplasms Caspase Mice Inbred C3H biology Prostatic Neoplasms Articles medicine.disease prostate cancer Xenograft Model Antitumor Assays 030104 developmental biology Proto-Oncogene Proteins c-bcl-2 030220 oncology & carcinogenesis Caspases Cancer cell Cancer research biology.protein cytotoxicity Taxoids Drug Screening Assays Antitumor medicine.drug |
| Zdroj: | International Journal of Oncology |
| ISSN: | 1791-2423 1019-6439 |
| Popis: | Docetaxel is a useful chemotherapeutic agent for the first-line treatment of hormone-refractory prostate cancer. Abnormal expression of Bcl-2 is commonly found in cancer cells, which increases their anti-apoptotic potency and chemo-resistance. We investigated the effects of Bcl-2 expression status on the susceptibility of DU145 cells, an androgen-independent human prostate cancer cell line, to docetaxel and other anticancer agents. A panel of Bcl-2-expressing DU145 cell lines was established. Bcl-2 expression levels were unrelated to the susceptibility of DU145 cells to docetaxel. The sensitivity of DU145 cells to cisplatin fluctuated, and the sensitivity to tumor necrosis factor (TNF)-α was decreased by Bcl-2 overexpression. In a xenograft mouse model, overexpression of Bcl-2 drastically decreased the sensitivity of DU145 cells to cisplatin and TNF-α; however, there was no change in the response to docetaxel. Fluorescent microscopy revealed that Bcl-2-overexpression had no effect on the docetaxel-induced death of DU145 cells, but significantly decreased DU145 cell death induced by cisplatin or TNF-α. Interestingly, docetaxel hardly induced caspase-3/7 activation in control or Bcl-2-overexpressing DU145 cells, but did at a low level in LNCaP cells, another prostate cancer cell line. Moreover, in contrast to LNCaP cells, the reduced viabilities of docetaxel-treated control and Bcl-2-overexpressing DU145 cells were not restored by the addition of either a Bid inhibitor or a panel of pro-apoptotic caspase inhibitors. These findings indicate that the antitumor effects of docetaxel on DU145 cells are independent of both Bcl-2 and pro-apoptotic caspases. |
| Databáze: | OpenAIRE |
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