Ultrasound activates ataxia telangiectasia mutated- and rad3-related (ATR)-checkpoint kinase 1 (Chk1) pathway in human leukemia Jurkat cells

Ultrasonics Sonochemistry
Yukihiro FurusawaTakashi Kondo

Abstract

Low-intensity ultrasound (US) has been shown to induce death of cancer cells; however, the underlying mechanism remains unclarified. Here, we provide novel evidence that the inhibition of checkpoint kinase 1 (Chk1) by a selective inhibitor or small interfering RNA (siRNA) enhances US-induced apoptosis in Jurkat cells. Jurkat cells showed insignificant lysis immediately after US at any applied intensity, whereas approximately 70% of the cells were γH2AX-positive 30min after US at 0.4W/cm(2). Regarding DNA damage response (DDR), Chk1, known as a target of ataxia telangiectasia mutated (ATM) and rad3-related (ATR), was phosphorylated in cells after US exposure. An ATM inhibitor showed nearly no effect on Chk1 phosphorylation, whereas chemicals showing the ATR inhibitory effect markedly abrogated the phosphorylation, indicating that Chk1 phosphorylation is preferentially more dependent on ATR than on ATM in cells exposed to US. The pharmacological inhibition of Chk1 promoted caspase-3 cleavage and increased the percentage of cells in SubG1 after US exposure. siRNA targeting Chk1 abrogated approximately 55% of Chk1 expression and also promoted apoptosis, suggesting that Chk1 plays anti-apoptotic roles in response to US. These findin...Continue Reading

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