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

A. Enomoto, N. Suzuki, Y. Kang, K. Hirano, Y. Matsumoto, J. Zhu, A. Morita, Y. Hosoi, K. Sakai, H. Koyama

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)589-600
Number of pages12
JournalInternational Journal of Radiation Biology
Volume79
Issue number8
DOIs
Publication statusPublished - 2003 Aug
Externally publishedYes

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

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