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Issue 12, 2007
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Apoptotic and autophagic responses to Bcl-2 inhibition and photodamage

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Abstract

Among the cellular responses to photodamage initiated by photodynamic therapy (PDT) are autophagy and apoptosis. While autophagy is a reversible process that can be both a survival and a death pathway, apoptosis is irreversible, leading only to cell death. In this study, we followed the fate of mouse leukemia L1210 cells after photodamage to the endoplasmic reticulum (ER) using a porphycene photosensitizer, where Bcl-2 was among the PDT targets. In wild-type cells, we observed a rapid wave of autophagy, presumed to represent the recycling of some damaged organelles, followed by apoptosis. Using shRNA technology, we created a Bax knockdown line (L1210/Bax). In the latter cell line, we found a marked decrease in apoptosis after photodamage or pharmacologic inactivation of Bcl-2 function, but this did not affect PDT efficacy. Loss of viability was associated with a highly-vacuolated morphology consistent with autophagic cell death. Previous studies indicated pro-survival attributes of autophagy after low-dose PDT, suggesting that autophagy may be responsible for the ‘shoulder’ on the dose-response curve. It appears that attempts at extensive recycling of damaged organelles are associated with cell death, and that this phenomenon is amplified when apoptosis is suppressed.

Graphical abstract: Apoptotic and autophagic responses to Bcl-2 inhibition and photodamage

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Publication details

The article was received on 25 May 2007, accepted on 19 Jul 2007 and first published on 30 Jul 2007


Article type: Paper
DOI: 10.1039/B707953B
Citation: Photochem. Photobiol. Sci., 2007,6, 1290-1295
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    Apoptotic and autophagic responses to Bcl-2 inhibition and photodamage

    D. Kessel and A. S. Arroyo, Photochem. Photobiol. Sci., 2007, 6, 1290
    DOI: 10.1039/B707953B

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