5-ALA mediated photodynamic therapy induces autophagic cell death via AMP-activated protein kinase.
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.
Ji
Hong-Tai
HT
Department of Biochemical Science and Technology, National Taiwan University, Taipei 106, Taiwan. r92450015@ntu.edu.tw
Chien
Li-Ting
LT
Lin
Yu-Hsin
YH
Chien
Hsiung-Fei
HF
Chen
Chin-Tin
CT
D000263:Adenylate Kinase / Q000187:drug effects* / Q000378:metabolism; D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D015151:Immunoblotting; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014162:Transfection
D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid; D000263:Adenylate Kinase