Sign up for Table of Contents Alerts.
Email this page
Print this page
Research Paper
The Functional Effects of Acid Ceramidase Over-Expression in Prostate Cancer Progression and Resistance to Chemotherapy
Antonio F. Saad, William D. Meacham, Aiping Bai, Viviane Anelli, Viviane Anelli, Ayman E.M. Mahdy, Lorianne S. Turner, Joe Cheng, Alicja Bielawska, Jacek Bielawski, Thomas E. Keane, Lina M. Obeid, Yusuf A. Hannun, James S. Norris and Xiang Liu
volume 6 | issue 9
September 2007Pages: 1455 - 1460
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.
Among the many processes regulating cell death, ceramide signaling is a vital component. We previously determined that acid ceramidase (AC) is upregulated in 60% of primary prostate cancer (PCa) tissues, suggesting that AC may play a role in tumor development. In order to determine the significance of AC elevation, stable clones of DU145 cells with AC over-expression (AC-EGFP) were generated. Compared to controls (EGFP), AC-EGFP cells exhibited enhanced cell proliferation and migration. Subcutaneous injection of AC-EGFP cells into Nu/Nu mice resulted in larger tumor volumes compared to EGFP controls. Moreover, using the MTS viability assay, AC-EGFP cells were more resistant to cell death induced by doxorubicin, cisplatin, etoposide, gemcitabine or C6-ceramide. Conversely, knock down of AC using siRNA, sensitized AC-EGFP cells to these drugs. In addition, mass spectroscopic analysis of sphingolipids indicated that long chain ceramide levels were decreased in AC-EGFP cells treated with either doxorubicin or etoposide. In conclusion, this study implicates AC as a critical regulator of PCa progression by affecting not only tumor cell proliferation and migration but also responses to drug therapy, suggesting AC as a potential therapeutic target in advanced PCa.
Authors
Antonio F. Saad
Departments of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina
William D. Meacham
Departments of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina
Aiping Bai
Departments of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, South Carolina
Viviane Anelli
Departments of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, South Carolina
Viviane Anelli
Departments of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina
Ayman E.M. Mahdy
Departments of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina
Lorianne S. Turner
Departments of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina
Joe Cheng
Departments of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina
Alicja Bielawska
Departments of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, South Carolina
Jacek Bielawski
Departments of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, South Carolina
Thomas E. Keane
Department of Urology, Medical University of South Carolina, Charleston, South Carolina
Lina M. Obeid
Departments of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, South Carolina
Yusuf A. Hannun
Departments of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, South Carolina
James S. Norris
Medical University of South Carolina; Charleston, South Carolina
Xiang Liu
Departments of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.