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

作者：Francois Aurelie^*; Marchal Sophie; Guillemin Francois; Bezdetnaya Lina

来源：International Journal of Oncology, 2011, 39(6): 1537-1543.

DOI：10.3892/ijo.2011.1174

• photodynamic therapy
• mTHPC
• autophagy
• apoptosis
• ER oxidative stress
• caspases

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 mTH PC-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-I I, 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-VA D-FMK, the use of autophagy inhibitor, Wortmann in, impaired cytotox icity along with an increase in caspase-7 activation. These results demonstrate a valuable contribution of autophagy to cell death in mTH PC-photosensitized MCF-7 cells.

• 出版日期2011-12