Decreased c‐Myc expression and its involvement in X‐ray‐induced apoptotic cell death of human T‐cell leukaemia cell line MOLT‐4

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Abstract
Purpose: To investigate the possible involvement of c‐Myc and ceramide‐c‐Jun N‐terminal kinase (JNK) pathway in X‐ray‐induced apoptotic cell death of MOLT‐4 cells. Materials and methods: The expressions of c‐Myc protein and c‐myc mRNA after X‐irradiation were analysed by Western blotting and RT‐PCR between radiosensitive MOLT‐4 and radioresistant variant Rh‐1a cells with less JNK activation than the parental cells. Apoptotic cell death was determined by a dye exclusion test, the appearance of chromatin condensation and DNA fragmentation. The effect of a JNK activator anisomycin or c‐Myc inhibitor peptides (Int‐H1‐S6A, F8A) on the amount of c‐Myc protein and on the induction of apoptosis was investigated, respectively. Results: In X‐irradiated MOLT‐4 cells, amounts of both c‐myc mRNA and c‐Myc protein rapidly decreased, which was followed by apoptotic cell death, while little change or limited reduction of c‐Myc protein was observed in X‐irradiated Rh‐1a cells with accompanying higher cell viability. Exposure of MOLT‐4 and Rh‐1a cells to c‐Myc inhibitor peptides similarly induced apoptotic cell death with decreases of c‐Myc protein. Anisomycin rapidly induced JNK activation and a subsequent decrease of c‐Myc protein, causing cell death in MOLT‐4 cells. On the other hand, Rh‐1a cells were more resistant to anisomycin than parental MOLT‐4 cells, showing less JNK activation and a delayed decrease of c‐Myc protein. Conclusion: A decrease of c‐Myc protein was considered important in X‐ray‐induced apoptotic cell death of MOLT‐4 cells; activation of the JNK pathway caused reduction in the amounts of c‐myc mRNA and c‐Myc protein, and finally induced apoptotic cell death.