Journal
ONCOGENE
Volume 30, Issue 45, Pages 4544-4556Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2011.168
Keywords
high-content screen; autophagy; cell death; systematic analysis; cancer therapy
Funding
- Ligue Nationale contre le Cancer (Equipes labellisee)
- Agence Nationale pour la Recherche (ANR)
- European Commission
- Fondation pour la Recherche Medicale (FRM)
- Fondation Bettencourt-Schueller
- Institut National du Cancer (INCa)
- Canceropole Ile-de-France
- European Commission Apo-Sys
- La Ligue contre le Cancer
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To address the question of whether established or experimental anticancer chemotherapeutics can exert their cytotoxic effects by autophagy, we performed a high-content screen on a set of cytotoxic agents. We simultaneously determined parameters of autophagy, apoptosis and necrosis on cells exposed to similar to 1400 compounds. Many agents induced a 'pure' autophagic, apoptotic or necrotic phenotype, whereas less than 100 simultaneously induced autophagy, apoptosis and necrosis. A systematic analysis of the autophagic flux induced by the most potent 80 inducers of GFP-LC3 puncta among the NCI panel agents showed that 59 among them truly induced autophagy. The remaining 21 compounds were potent inducers of apoptosis or necrosis, yet failed to stimulate an autophagic flux, which were characterized as microtubule inhibitors. Knockdown of ATG7 was efficient in preventing GFP-LC3 puncta, yet failed to attenuate cell death by the agents that induce GFP-LC3 puncta. Thus there is not a single compound that would induce cell death by autophagy in our screening, underscoring the idea that cell death is rarely, if ever, executed by autophagy in human cells. Oncogene (2011) 30, 4544-4556; doi: 10.1038/onc.2011.168; published online 16 May 2011
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