5-ALA mediated photodynamic therapy induces autophagic cell death via AMP-activated protein kinase

Hong-Tai Ji, Li-Ting Chien, Yu-Hsin Lin, Hsiung-Fei Chien, Chin-Tin Chen

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Photodynamic therapy (PDT) has been developed as an anticancer treatment, which is based on the tumor-specific accumulation of a photosensitizer that induces cell death after irradiation of light with a specific wavelength. Depending on the subcellular localization of the photosensitizer, PDT could trigger various signal transduction cascades and induce cell death such as apoptosis, autophagy, and necrosis. In this study, we report that both AMP-activated protein kinase (AMPK) and mitogen-activated protein kinase (MAPK) signaling cascades are activated following 5-aminolevulinic acid (ALA)-mediated PDT in both PC12 and CL1-0 cells. Although the activities of caspase-9 and -3 are elevated, the caspase inhibitor zVAD-fmk did not protect cells against ALA-PDT-induced cell death. Instead, autophagic cell death was found in PC12 and CL1-0 cells treated with ALA-PDT. Most importantly, we report here for the first time that it is the activation of AMPK, but not MAPKs that plays a crucial role in mediating autophagic cell death induced by ALA-PDT. This novel observation indicates that the AMPK pathway play an important role in ALA-PDT-induced autophagy. © 2010 Ji et al; licensee BioMed Central Ltd.
Original languageEnglish
JournalMolecular Cancer
Volume9
DOIs
Publication statusPublished - 2010
Externally publishedYes

Keywords

  • aminolevulinic acid
  • caspase 3
  • caspase 9
  • hydroxymethylglutaryl coenzyme A reductase kinase
  • mitogen activated protein kinase
  • mitogen activated protein kinase p38
  • stress activated protein kinase
  • adenylate kinase
  • photosensitizing agent
  • animal cell
  • article
  • autophagy
  • cancer cell
  • controlled study
  • DNA fragmentation
  • enzyme activation
  • human
  • human cell
  • mitochondrial membrane potential
  • nonhuman
  • oxidative stress
  • photodynamic therapy
  • survival rate
  • animal
  • drug effect
  • genetic transfection
  • immunoblotting
  • metabolism
  • methodology
  • mitochondrion
  • pathology
  • photochemotherapy
  • physiology
  • rat
  • signal transduction
  • Adenylate Kinase
  • Aminolevulinic Acid
  • Animals
  • Autophagy
  • DNA Fragmentation
  • Immunoblotting
  • MAP Kinase Signaling System
  • Membrane Potential, Mitochondrial
  • Mitochondria
  • Oxidative Stress
  • Photochemotherapy
  • Photosensitizing Agents
  • Rats
  • Signal Transduction
  • Transfection

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