Paper Title:
N-Acetylphytosphingosine Enhances the Radiosensitivity of Tumor Cells by Increasing Apoptosis
  Abstract

Ceramides are well-known second messengers which mediate apoptosis, proliferation, differentiation in mammalian cells, but the physiological roles of phytosphingosines are poorly understood. We hypothesized that one of the phytosphingosine derivatives, N-acetylphytosphingosine (NAPS) can induce apoptosis in human leukemia Jurkat cell line and increase apoptosis in irradiated MDA-MB-231 cells. We first examined the effect of NAPS on apoptosis of Jurkat cells. NAPS had a more rapid and stronger apoptotic effect than C2-ceramide in Jurkat cells and significant increase of apoptosis was observed at 3 h after treatment. In contrast, the apoptosis induced by C2-ceramide was observed only after 16 h of treatment. NAPS induced apoptosis was mediated by caspase 3 and 8 activation and inhibited by z-VAD-fmk. Ceramide plays a pivotal role in radiation induced apoptosis. We postulated that exogenous treatment of NAPS sensitizes tumor cells to ionizing radiation, since NAPS might be used as a more effective alternative to C2-ceramide. As expected, NAPS decreased clonogenic survival of irradiated MDA-MB-231 cells dose dependently, and apoptosis of irradiated cells in the presence of NAPS was increased through the caspase activation. Taken together, NAPS is an effective apoptosis-inducing agent, which can be readily synthesized from yeast sources, and is a potent alternative to ceramide for the further study of ceramide associated signaling and the development of radiosensitizing agent.

  Info
Periodical
Key Engineering Materials (Volumes 277-279)
Edited by
Kwang Hwa Chung, Yong Hyeon Shin, Sue-Nie Park, Hyun Sook Cho, Soon-Ae Yoo, Byung Joo Min, Hyo-Suk Lim and Kyung Hwa Yoo
Pages
536-541
DOI
10.4028/www.scientific.net/KEM.277-279.536
Citation
Y. S. Han, Y. H. Kim, Y. S. Yun, S. J. Jeon, K. S. Kim, S. H. Hong, C. S. Park, J. Y. Song, "N-Acetylphytosphingosine Enhances the Radiosensitivity of Tumor Cells by Increasing Apoptosis", Key Engineering Materials, Vols. 277-279, pp. 536-541, 2005
Online since
January 2005
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