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

Molecular Cancer

Research

Hsiung-Fei Chien¹  Hong-Tai Ji²  Yu-Hsin Lin²  Chin-Tin Chen³  Li-Ting Chien³ 

[1]Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, 100, Taipei, Taiwan

[2]Department of Surgery, National Taiwan University College of Medicine, 100, Taipei, Taiwan

[3]Department of Biochemical Science and Technology, National Taiwan University, 106, Taipei, Taiwan

[4]Department of Biochemical Science and Technology, National Taiwan University, 106, Taipei, Taiwan

[5]Center for Optoelectronic Biomedicine, National Taiwan University College of Medicine, 100, Taipei, Taiwan

关键词: PC12 Cell;    Mitochondrial Membrane Potential;    Extracellular Signal Regulate Kinase;    AMPK Activation;    Autophagic Cell Death;   

DOI  :  10.1186/1476-4598-9-91

 received in 2009-12-16, accepted in 2010-04-28,  发布年份 2010

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Ji et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.