Autophagy is increased in prostate cancer cells overexpressing acid ceramidase and enhances resistance to C6 ceramide
| Autor: | James S. Norris, Xiang Liu, Thomas E. Keane, Joe Cheng, Lorianne S. Turner, Thomas H. Beckham |
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| Rok vydání: | 2010 |
| Předmět: |
Male
autophagy Cancer Research Ceramide Acid Ceramidase Urology Antineoplastic Agents Biology Ceramides Article 03 medical and health sciences chemistry.chemical_compound Prostate cancer 0302 clinical medicine Cell Line Tumor medicine Humans ceramide 030304 developmental biology 0303 health sciences sphingolipids Sphingosine Autophagy apoptosis Prostatic Neoplasms Lipid signaling prostate cancer medicine.disease Sphingolipid 3. Good health Oncology Biochemistry chemistry Drug Resistance Neoplasm Apoptosis 030220 oncology & carcinogenesis Cancer research |
| Zdroj: | Prostate cancer and prostatic diseases |
| ISSN: | 1476-5608 1365-7852 |
| DOI: | 10.1038/pcan.2010.47 |
| Popis: | Acid ceramidase (AC) over-expression has been observed in prostate cancer cell lines and primary tumors, and contributes to resistance to chemotherapy and radiation. The consequence of AC over-expression is the ability to convert ceramide, which is often produced as a pro-apoptotic response to stress, to sphingosine, which can then be converted to the pro-survival molecule sphingosine-1-phosphate. In addition to their ability to metabolize ceramide produced in response to stress, we show here that prostate cancer cell lines over-expressing acid ceramidase also have increased lysosomal density and increased levels of autophagy. Furthermore, pre-treatment with 3-methyladenine restores sensitivity of these cells to treatment with C6-ceramide. We also observed increased expression of the lysosomal stabilizing protein KIF5B and increased sensitivity to the lysosomotropic agent LCL385. Thus, we conclude that acid ceramidase over-expression increases autophagy in prostate cancer cells, and that increased autophagy enhances resistance to ceramide. |
| Databáze: | OpenAIRE |
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