Papers by Author: Sung Hee Hong

Abstract: An immunomodulator ginsan, polysaccharide isolated from Panax ginseng, showed a mitogenic activity, generation of LAK cells, and the secretion of several cytokines. In the present study, we evaluated the protective effects of in vivo injected ginsan against irradiation. Ginsan was found to significantly increase the number of bone marrow cells, spleen cells and the number of circulating neutrophils, lymphocytes and platelets in irradiated mice. In addition, ginsan induced the production of a variety of cytokines such as IL-1, IL-6, IL-12, TNF-a and SCF, which are required for a hematopoietic recovery and are closely correlated with the antioxidant defense systems. We demonstrated that the pretreatment with ginsan protected the mice from the lethal effects of ionizing radiation more effectively than given after the irradiation. A dramatic increase of the survival of the ginsan-treated group from LD50/30 7.54 Gy of the PBS-control group to 10.93 Gy was observed. Moreover, the levels of the antioxidant enzymes such as superoxide dismutase (SOD), catalase and gluthathion peroxidase (GPx) were increased 1.5-2 fold in the ginsan treated mice compared to the irradiated mice. In conclusion, our data suggests that the radioprotective action of ginsan in the irradiated mice may be due to not only to the rapid regeneration of hematopoietic cells but also to the modulation of antioxidant defense systems.

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.