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

Yukihiro Furusawa, Takashi Iizumi, Yoshisada Fujiwara, Mariame Ali Hassan, Yoshiaki Tabuchi, Takaharu Nomura, Takashi Kondo

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 30 min after US at 0.4 W/cm2. 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 findings revealed, for the first time, that US activates Chk1 dependently on ATR and the activated Chk1 is involved in apoptosis of cells exposed to US. Moreover, we propose that Chk1 may be a promising target in US-aided therapy.

Original languageEnglish
Pages (from-to)1246-1251
Number of pages6
JournalUltrasonics Sonochemistry
Volume19
Issue number6
DOIs
Publication statusPublished - 2012 Nov

Keywords

  • ATR
  • Apoptosis
  • Chk1
  • DNA damage
  • Ultrasound

ASJC Scopus subject areas

  • Chemical Engineering (miscellaneous)
  • Environmental Chemistry
  • Radiology Nuclear Medicine and imaging
  • Acoustics and Ultrasonics
  • Organic Chemistry
  • Inorganic Chemistry

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