Radiation-induced autophagy in normal and cancer cells: Towards novel cytoprotection and radio-sensitization policies?

Zois, Christos E.; Koukourakis, Michael I.

doi:10.4161/auto.5.4.7667

Cited by 123 publications

(105 citation statements)

References 83 publications

(120 reference statements)

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“…32 Our previous studies show that MDA-MB-231-2A (PTTG1-knockdown) and MCF-7 (low PTTG1 expression) breast cancer cells senesce after irradiation, which enhances the radiosensitivity of the cells. 12,13 Although senescence definitely accounts for the radiation-induced phenotype, additional pathways, such as autophagy, may be of equal importance.…”

Section: Discussionmentioning

confidence: 99%

Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells

et al. 2014

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“…Although radiation therapy is thought to exert its cytotoxic effects mainly by inducing oxidative stress, the role of autophagy in radiation therapy has been exhaustively covered in a recent review 124 and will not be further discussed here.…”

Section: Sod Catalase and Gsh Reductase Mimeticmentioning

confidence: 99%

ROS-mediated mechanisms of autophagy stimulation and their relevance in cancer therapy

Dewaele¹,

Maes²,

Agostinis³

2010

Autophagy

274

199

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“…Anticancer agents induce cell death in cancer and normal cells via mechanisms including apoptosis and autophagy (1)(2)(3)(4). Therefore, there is a need for alternative anticancer agents that can promote cancer cell death while avoiding killing of normal, non-cancerous cells.…”

mentioning

confidence: 99%

Resveratrol Induces p53-independent, X-linked Inhibitor of Apoptosis Protein (XIAP)-mediated Bax Protein Oligomerization on Mitochondria to Initiate Cytochrome c Release and Caspase Activation

Gogada¹,

Prabhu²,

Amadori

et al. 2011

Journal of Biological Chemistry

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Resveratrol, a naturally occurring phytoalexin, is known to induce apoptosis in multiple cancer cell types, but the underlying molecular mechanisms remain unclear. Here, we show that resveratrol induced p53-independent, X-linked inhibitor of apoptosis protein (XIAP)-mediated translocation of Bax to mitochondria where it underwent oligomerization to initiate apoptosis. Resveratrol treatment promoted interaction between Bax and XIAP in the cytosol and on mitochondria, suggesting that XIAP plays a critical role in the activation and translocation of Bax to mitochondria. This process did not involve p53 but required accumulation of Bim and t-Bid on mitochondria. Bax primarily underwent homo-oligomerization on mitochondria and played a major role in release of cytochrome c to the cytosol. Bak, another key protein that regulates the mitochondrial membrane permeabilization, did not interact with p53 but continued to associate with Bcl-xL. Thus, the proapoptotic function of Bak remained suppressed during resveratrol-induced apoptosis. Caspase-9 silencing inhibited resveratrol-induced caspase activation, whereas caspase-8 knockdown did not affect caspase activity, suggesting that resveratrol induces caspase-9-dependent apoptosis. Together, our findings characterize the molecular mechanisms of resveratrol-induced caspase activation and subsequent apoptosis in cancer cells.Anticancer agents induce cell death in cancer and normal cells via mechanisms including apoptosis and autophagy (1-4). Therefore, there is a need for alternative anticancer agents that can promote cancer cell death while avoiding killing of normal, non-cancerous cells. Resveratrol (trans-3,5,4Ј-trihydroxystilbene) is a naturally occurring polyphenolic phytoalexin found at high levels in the skin of grapes and in red wine. It is also present in peanuts and other plant products. Resveratrol has been shown to possess an apoptosis-dependent anticancer activity and minimal toxicity to normal cells (5-11). How resveratrol induces apoptosis or cancer cell death is not clearly known, but available evidence indicates that resveratrol induces p53-dependent signaling, which leads to cell cycle arrest and apoptosis induction (10, 12, 13). Additionally, resveratrol targets mitochondria to induce cytochrome c release and thereby triggers caspase-dependent apoptotic cell death in multiple types of cancer cells (14 -18). How resveratrol induces cytochrome c release and caspase activation to execute apoptosis remains unclear.Caspases are activated by proteolytic processing and are broadly divided into initiator caspases (e.g. procaspase-8 and -9) and executioner caspases (such as procaspase-3 and -7) (19 -22). During apoptosis, the released cytochrome c from mitochondria triggers caspase-9 activation, whereas ligation of death receptors on the plasma membrane activates caspase-8. Active caspase-8 generated upon death receptor ligation requires Bid-mediated cytochrome c release to execute apoptotic cell death in epithelial cancer cells (22)(23)(24)(25). Proapoptotic BH3-o...

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Radiation-induced autophagy in normal and cancer cells: Towards novel cytoprotection and radio-sensitization policies?

Cited by 123 publications

References 83 publications

Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells

Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells

ROS-mediated mechanisms of autophagy stimulation and their relevance in cancer therapy

Resveratrol Induces p53-independent, X-linked Inhibitor of Apoptosis Protein (XIAP)-mediated Bax Protein Oligomerization on Mitochondria to Initiate Cytochrome c Release and Caspase Activation

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