mTHPC-based photodynamic therapy induction of autophagy and apoptosis in cultured cells in relation to mitochondria and endoplasmic reticulum stress

  • Authors:
    • Aurélie François
    • Sophie Marchal
    • François Guillemin
    • Lina Bezdetnaya
  • View Affiliations

  • Published online on: August 24, 2011     https://doi.org/10.3892/ijo.2011.1174
  • Pages: 1537-1543
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Abstract

Photodynamic therapy (PDT), an approved anticancer treatment, is reported as a potent inducer of programmed cell death (PCD) by both apoptosis and autophagy. The present study investigated the kinetics of both autophagy and caspase activation in MCF-7 cells submitted to mTHPC-PDT upon condition of treatment promoting ER accumulation of mTHPC. Fluence-dependent immediate cytochrome c (cyt C) release followed by caspase-9 and -7 activation at 1 h post-PDT evidenced a mitochondrial oxidative stress triggered by high light doses leading to >90% of cell death. ER oxidative stress was monitored by the induction of the glucose-related protein chaperone GRP78. From 6 h post-PDT, GRP78 induction was accompanied by the conversion of LC3-I into LC3-II, the hallmark of autophagosome formation. The formation of acid vesicles evidenced by fluorescence microscopy was obvious from 22 h post-PDT. Twenty-four hours post-PDT, cyt C release decreased and caspase-9 cleavage disappeared, while the expression of cleaved caspase-7 remained significant. At the same time, the profiles of GRP78, cleaved caspase-7 and LC3-II expression were similar irrespective of light doses. In contrast to an inhibitor of caspase activation Z-VAD-FMK, the use of autophagy inhibitor, Wortmannin, impaired cytotoxicity along with an increase in caspase-7 activation. These results demonstrate a valuable contribution of autophagy to cell death in mTHPC-photosensitized MCF-7 cells.

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December 2011
Volume 39 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
François, A., Marchal, S., Guillemin, F., & Bezdetnaya, L. (2011). mTHPC-based photodynamic therapy induction of autophagy and apoptosis in cultured cells in relation to mitochondria and endoplasmic reticulum stress. International Journal of Oncology, 39, 1537-1543. https://doi.org/10.3892/ijo.2011.1174
MLA
François, A., Marchal, S., Guillemin, F., Bezdetnaya, L."mTHPC-based photodynamic therapy induction of autophagy and apoptosis in cultured cells in relation to mitochondria and endoplasmic reticulum stress". International Journal of Oncology 39.6 (2011): 1537-1543.
Chicago
François, A., Marchal, S., Guillemin, F., Bezdetnaya, L."mTHPC-based photodynamic therapy induction of autophagy and apoptosis in cultured cells in relation to mitochondria and endoplasmic reticulum stress". International Journal of Oncology 39, no. 6 (2011): 1537-1543. https://doi.org/10.3892/ijo.2011.1174