title: Melatonin exerts differential actions on X-ray radiation-induced apoptosis in normal mice splenocytes and Jurkat leukemia cells.
abstract: The ability of melatonin as a potent antioxidant was used as a rationale for testing its antiapoptotic ability in normal cells. Recently, melatonin was shown to possess proapoptotic action by increasing reactive oxygen species in certain cancer cells. The modification of radiation-induced apoptosis by melatonin and the expression of apoptosis-associated upstream regulators were studied in normal mice splenocytes and Jurkat T leukemia cells. C57BL/6 mice were exposed to a single whole body X-ray radiation dose of 2 Gy with or without 250 mg/kg melatonin pretreatment. The Jurkat cells were divided into four groups of control, 1 mm melatonin alone, 4 Gy irradiation-only and melatonin pretreatment before irradiation. The highest level of apoptosis in the normal splenic white pulp was detected by TUNEL assay at 8 hr after irradiation. At this time, the apoptotic index of irradiation-only and melatonin pretreatment groups were 35.6% and 20.7%, respectively. This reduced apoptosis by melatonin was associated with the increase of Bcl-2 expression and a reduction of Bax/Bcl-2 ratio through a relative decrease of p53 mRNA and protein. In the Jurkat cells treated with a combination of melatonin and radiation, both Annexin V-FITC(+)/PI(-) and Annexin V-FITC(+) cells were increased at 48 hr after irradiation when compared with irradiation-only or melatonin alone. The expressions of p53 between groups were well correlated with the results of Annexin V binding. The irradiation or melatonin did not influence the JNK1 expression in Jurkat cells. The present results suggest that melatonin enhances radiation-induced apoptosis in Jurkat leukemia cells, while reducing radiation-induced apoptosis in normal mice splenocytes. These differential effects on radiation-induced apoptosis by melatonin might involve the regulation of p53 expression.
authors: Department of Radiation Oncology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors: Seong Soon
authors: SS
authors: Jang
authors: Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors: Won Dong
authors: WD
authors: Kim
authors: Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju, Korea.
authors: Woo-Yoon
authors: WY
authors: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006651:Histocytochemistry; D006801:Humans; D020287:In Situ Nick-End Labeling; D019169:Jurkat Cells; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014965:X-Rays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D048670:MAP Kinase Kinase 4; D008550:Melatonin