Melatonin exerts differential actions on X-ray radiation-induced apoptosis in normal mice splenocytes and Jurkat leukemia cells.
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.
Jang
Seong Soon
SS
Department of Radiation Oncology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Kim
Won Dong
WD
Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju, Korea.
Park
Woo-Yoon
WY
Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju, Korea.
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
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