Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy

M. Fukumoto, Y. Kuwahara, T. Oikawa, Y. Ochiai, M. H. Roudkenar, M. Fukamoto, T. Shimura, Y. Ohtake, Y. Ohkubo, S. Mori, M. A.Y. Uchiya

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Radiotherapy is a well-established treatment for cancer. However, the existence of radioresistant cells is one of the major obstacles in radiotherapy. In order to understand the mechanism of cellular radioresistance and develop more effective radiotherapy, we have established clinically relevant radioresistant (CRR) cell lines, which continue to proliferate under daily exposure to 2 Gray (Gy) of X-rays for4>30 days. X-ray irradiation significantly induced autophagic cells in parental cells, which was exiguous in CRR cells, suggesting that autophagic cell death is involved in cellular radiosensitivity. An autophagy inducer, rapamycin sensitized CRR cells to the level of parental cells and suppressed cell growth. An autophagy inhibitor, 3-methyladenine induced radioresistance of parental cells. Furthermore, inhibition of autophagy by knockdown of Beclin-1 made parental cells radioresistant to acute radiation. These suggest that the suppression of autophagic cell death but not apoptosis is mainly involved in cellular radioresistance. Therefore, the enhancement of autophagy may have a considerable impact on the treatment of radioresistant tumor.

Original languageEnglish
Article numbere177
JournalCell Death and Disease
Volume2
Issue number6
DOIs
Publication statusPublished - 2011 Jun

Keywords

  • 3-Methyladenine
  • Autophagy
  • Radioresistant cells
  • Radiotherapy
  • Rapamycin

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy'. Together they form a unique fingerprint.

  • Cite this

    Fukumoto, M., Kuwahara, Y., Oikawa, T., Ochiai, Y., Roudkenar, M. H., Fukamoto, M., Shimura, T., Ohtake, Y., Ohkubo, Y., Mori, S., & Uchiya, M. A. Y. (2011). Enhancement of autophagy is a potential modality for tumors refractory to radiotherapy. Cell Death and Disease, 2(6), [e177]. https://doi.org/10.1038/cddis.2011.56