Inhibition of DNA-dependent protein kinase promotes ultrasound-induced cell death including apoptosis in human leukemia cells

Yukihiro Furusawa, Yoshisada Fujiwara, Mariame Ali Hassan, Yoshiaki Tabuchi, Akinori Morita, Atsushi Enomoto, Takashi Kondo

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Ultrasound (US) has been shown to induce cell death in cancer cells; however, the underlying mechanism remains elusive. Here, we report a set of novel findings on the molecular mechanism. We found that Akt (also known as protein kinase B), a substrate of DNA-dependent protein kinase (DNA-PK), was phosphorylated in U937 cells nullified with p53 or Molt-4 cells artificially abrogated with p53 after US exposure. On the contrary, Akt phosphorylation was transiently down-regulated then recovered in Molt-4 cells harboring wild-type p53 in US-exposed cells, possibly due to a mutual regulation between p53 and Akt. Inhibition of ataxia-telangiectasia mutated (ATM) or DNA-PK revealed that DNA-PK, rather than ATM, was preferentially involved in Akt phosphorylation and cell survival after US-exposure in all cell lines. These results indicate that DNA-PK plays a protective role against US-induced cell death regardless of p53 phenotype. In conclusion, our findings provide the first delineation of the role of DNA-PK in US-induced cell death and suggest that targeting DNA-PK might be a promising strategy to augment cancer eradication by US.

Original languageEnglish
Pages (from-to)107-112
Number of pages6
JournalCancer Letters
Volume322
Issue number1
DOIs
Publication statusPublished - 2012 Sep 1

Keywords

  • ATM
  • Akt
  • Apoptosis
  • Cell death
  • DNA-PKcs
  • Ultrasound

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Furusawa, Y., Fujiwara, Y., Hassan, M. A., Tabuchi, Y., Morita, A., Enomoto, A., & Kondo, T. (2012). Inhibition of DNA-dependent protein kinase promotes ultrasound-induced cell death including apoptosis in human leukemia cells. Cancer Letters, 322(1), 107-112. https://doi.org/10.1016/j.canlet.2012.02.020