Apoptotic Effects of Dietary and Synthetic Sphingolipids in Androgen-Independent (PC-3) Prostate Cancer Cells |
| |
Authors: | Kyle D Kent Elizabeth A Clubbs W James Harper Joshua A Bomser |
| |
Affiliation: | (1) Department of Food Science and Technology, The Ohio State University, 2015 Fyffe Rd, Columbus , 43210-1097, OH, USA;(2) OSU Interdisciplinary PhD Program in Nutrition, The Ohio State University, Columbus, 43210, OH, USA;(3) Department of Human Nutrition, The Ohio State University, 1787 Neil Ave, 325 Campbell Hall, Columbus, 43210, OH, USA |
| |
Abstract: | Stress-induced activation and metabolism of plasma membrane sphingolipids results in intracellular ceramide accumulation and
has been shown to induce apoptosis in human prostate cancer cells. This effect has been observed using synthetic ceramide
analogs, such as C6-ceramide; however, the effects of naturally-occurring sphingolipids, such as C18-ceramide and sphingomyelin
(CerPCho), on apoptosis and prostate cancer cell proliferation have not been examined. The results of the present study demonstrate
that natural (CerPCho, C18-ceramide) and synthetic (C6-ceramide) sphingolipids reduced PC-3 cell proliferation by 15 ± 1.8,
17 ± 2.5, and 46 ± 2.1%, respectively (P < 0.05). These reductions in proliferation were due, in part, to increased cellular apoptosis. Treatment of PC-3 cells with
CerPCho and C18-ceramide significantly increased apoptosis by 3.0 ± 0.8 and 3.6 ± 0.6%, respectively, compared to the untreated
control, while the synthetic C6-ceramide significantly increased apoptosis by 55.7 ± 0.4%. C6-ceramide-induced apoptosis was
associated with cell cycle arrest in the G2/M phase, decreased extracellular signal-regulated kinase (ERK1/2) signaling and activation of the cell cycle regulatory protein,
retinoblastoma (pRb). Treatment of PC-3 cells with C18-ceramide and CerPCho did not alter cell cycle distribution, pRb or
ERK1/2 activation. Taken together, these results suggest that natural and synthetic sphingolipids induce apoptosis in PC-3
cells via distinct signaling mechanisms and potencies. |
| |
Keywords: | Apoptosis Cancer Ceramide Prostate Sphingomyelin |
本文献已被 PubMed SpringerLink 等数据库收录! |
|