Caffeine-suppressed ATM pathway leads to decreased p53 phosphorylation and increased programmed cell death in gamma-irradiated leukaemic molt-4 cells
Abstrakt
In this study we used caffeine, a non-specific ATM inhibitor, and studied its effect on the activation of the proteins involved in cell cycle control and the induction of apoptosis in human T-lymphocyte leukaemic MOLT-4 cells (p53 wt) after irradiation. We evaluated the expression of the tumour-suppressor p53, the cell cycle regulator p21, and the anti-apoptotic protein myeloid cell leukemia 1 (Mcl-1).
After treatment with 2 mM caffeine, the cells were irradiated by 1 or 3 Gy. The ATM/p53 pathway was suppressed, which led to increased apoptosis accompanied by a p53-independent decrease in Mcl-1.
It also caused down-regulation of p21, which possibly contributed to the shortened cell cycle arrest necessary for effective DNA repair and thus impeded radio-resistance. Caffeine promotes the cytotoxic effect of ionising radiation and provides a possible platform for the development of new anti-cancer therapeutics known as radio-sensitizers.