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N-Acetylphytosphingosine Enhances the Radiosensitivity of Tumor Cells by Increasing Apoptosis

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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.

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Periodical:

Key Engineering Materials (Volumes 277-279)

Pages:

536-541

DOI:

https://doi.org/10.4028/www.scientific.net/KEM.277-279.536

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Online since:

January 2005

Authors:

Young Soo Han, Yun Hwa Kim, Yeon Sook Yun, Soo Jin Jeon, Ki Sung Kim, Sung Hee Hong, Chang Soe Park, Jie Young Song

Keywords:

Apoptosis, N-Acetylphytosphingosine, Radiosensitivity

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© 2005 Trans Tech Publications Ltd. All Rights Reserved

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