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Ionizing radiation activates AMP-activated kinase (AMPK): a target for radiosensitization of human cancer cells

Toran Sanli1, Ayesha Rashid, Caiqiong Liu

  • 1Department of Oncology, Juravinski Cancer Center and McMaster University, Hamilton, Ontario, Canada.

International Journal of Radiation Oncology, Biology, Physics
|July 10, 2010
PubMed
Abstract

Insights

Ionizing radiation (IR) activates AMP-activated kinase (AMPK) in cancer cells, independent of LKB1. Targeting this ATM-AMPK-p21 pathway with metformin may enhance radiosensitization.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Signaling

Background:

  • Adenosine monophosphate (AMP)-activated kinase (AMPK) is a crucial energy sensor.
  • AMPK is regulated by the tumor suppressor LKB1 and activated by starvation and growth factors via ataxia-telangiectasia mutated (ATM).

Purpose of the Study:

  • To investigate the regulation of AMPK by ionizing radiation (IR).
  • To explore AMPK's role in radiosensitization of human cancer cells.

Main Methods:

  • Human lung, prostate, and breast cancer cells were exposed to IR.
  • Cells were treated with ATM or AMPK inhibitors, or the AMPK activator metformin.
  • Analyses included immunoblotting, immunofluorescence, clonogenic survival assays, and cell cycle analysis.

Main Results:

  • IR robustly activated AMPK in all tested cancer cells, independent of LKB1.
  • ATM inhibition blocked IR-induced AMPK activation.
  • AMPK inhibition disrupted IR-induced p53/p21(waf/cip) expression and G2/M arrest, conferring IR resistance.
  • Metformin enhanced IR-induced AMPK activation and reduced cancer cell survival.

Conclusions:

  • IR activates AMPK in human cancer cells via an LKB1-independent pathway.
  • The ATM-AMPK-p21(waf/cip) pathway regulates cell cycle and survival post-IR.
  • Targeting AMPK with metformin shows potential for enhancing cancer cell radiosensitization.

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