C16 ceramide accumulates following androgen ablation in LNCaP prostate cancer cells.
Publication/Presentation Date
9-15-2003
Abstract
BACKGROUND: Adenocarcinoma of the prostate is the most frequently diagnosed non-cutaneous cancer and the second leading cause of cancer-related deaths among men in the United States. The most successful therapies to date for this tumor have involved some form of androgen ablation. However, these therapies become ineffective as the tumor evolves to an androgen-insensitive state. Ceramide is a lipid second messenger that has been shown to mediate growth arrest or cell death when added exogenously to prostate cancer cells. As a first step toward understanding the events that lead to the transition of prostate cancer cells to an androgen-independent state, we considered investigating the effect of androgen ablation on endogenous ceramide levels in androgen-sensitive and androgen-insensitive prostate cancer cells.
METHODS: To investigate the mechanisms of growth arrest/apoptosis in androgen-sensitive (LNCaP) and insensitive (DU-145, PC-3) cells, we used various methods including nonyl acridine orange (NAO) staining, propidium iodide (PI) staining/cell-cycle analysis, lipid analysis, and Western blotting assays.
RESULTS: In this study, we demonstrate that androgen ablation drives G(0)/G(1)-phase cell-cycle arrest followed by progressive apoptosis in vitro, in LNCaP cells. Lipid analysis indicated an increase in C16 ceramide, which was generated via the de novo pathway as revealed by blockade of ceramide synthase by fumonisin B1. The addition of 5alpha-dihydrotestosterone (DHT) or fumonisin B1 rescued LNCaP cells from apoptosis induced by androgen ablation, and decreased levels of intracellular C16 ceramide. Neither apoptosis nor an increase in C16 ceramide was observed in androgen-independent cell lines following androgen ablation.
Volume
57
Issue
1
First Page
66
Last Page
79
ISSN
0270-4137
Published In/Presented At
Eto, M., Bennouna, J., Hunter, O. C., Hershberger, P. A., Kanto, T., Johnson, C. S., Lotze, M. T., & Amoscato, A. A. (2003). C16 ceramide accumulates following androgen ablation in LNCaP prostate cancer cells. The Prostate, 57(1), 66–79. https://doi.org/10.1002/pros.10275
Disciplines
Medicine and Health Sciences
PubMedID
12886525
Department(s)
Fellows and Residents
Document Type
Article