Radiation-induced autophagy is associated with LC3 and its inhibition sensitizes malignant glioma cells

Ito, Hiroki; Daido, Shigeru; Kanzawa, Takao; Kondo, Seiji; Kondo, Yasuko

doi:10.3892/ijo.26.5.1401

Cited by 182 publications

(193 citation statements)

References 0 publications

Supporting

Mentioning

183

Contrasting

Unclassified

Order By: Relevance

“…37,38 The localization of GFP-LC3 was used to detect autophagosomes by confocal microscopy. 37,38,42,43 A diffuse distribution of GFP-LC3 could be observed in the absence of TAU, and a massive punctated pattern in the presence, which is known to be caused by the localization of LC3-II on the autophagosome membrane (Fig. 4A).…”

Section: Discussionmentioning

confidence: 97%

The antibacterial substance taurolidine exhibits anti-neoplastic action based on a mixed type of programmed cell death

Stendel¹,

Biefer²,

Dékány³

et al. 2009

Autophagy

View full text Add to dashboard Cite

The antibacterial amino-acid derivative taurolidine (TAU) has been recently shown to exhibit anti-neoplastic activity based on a mechanism, which is still unknown in detail. Cytotoxicity and clonogenic assays were performed and the impact of apoptosis modulators, a radical scavenger, autophagy inhibitors, silencing of apoptosis inducing actor (AIF) and cytochrome-c (Cyt-C) by siRNA, and knockdown of autophagy related genes were evaluated in vitro. The intracellular ATP-content, release of AIF and Cyt-C, and DNA-laddering were investigated. This study could demonstrate cell killing, inhibition of proliferation, and inhibition or prevention of colony formation in human glioma cell lines and ex vivo glioblastoma cells after incubation with TAU. This effect is based on the induction of a mixed type of programmed cell death with the main preference of autophagy, and involvement of senescence, necroptosis and necrosis. This mechanism of action may open a new approach for therapeutic intervention.

show abstract

Section: Discussionmentioning

confidence: 97%

The antibacterial substance taurolidine exhibits anti-neoplastic action based on a mixed type of programmed cell death

Stendel¹,

Biefer²,

Dékány³

et al. 2009

Autophagy

View full text Add to dashboard Cite

show abstract

“…Accordingly, inhibition of autophagy in breast, prostate and colon cancer cells, and in malignant glioma cells enhanced the death response of these cells to radiotherapy. 31,32 Likewise, inhibition of autophagy increased the antineoplastic potency of the histone deacetylase inhibitor SAHA in imatinib-resistant primary CML cells 34 and the antiangiogenic effects of kringle 5 in endothelial cells, by activating apoptotic cell death. 35 Furthermore, mitophagy may directly limit apoptosis by preventing MOMP and the subsequent release of pro-apoptotic molecules such as cytochrome C and Smac/Diablo.…”

Section: Conceptual Cross-talkmentioning

confidence: 99%

“…26,27 Autophagy was also shown to protect non-transformed epithelial cells from anoikis, the loss of matrix attachment that induces apoptotic cell death. 28 Autophagy is also a mechanism to maintain genomic integrity in the face of metabolic stress, drug treatment or radiation damage, [29][30][31][32] for example, by scavenging depolarized mitochondria that are a source for genotoxic ROS, a process known as mitophagy. 33 Consistent with this, in the absence of autophagy, DNA damage, gene amplification and chromosomal abnormalities were evident following metabolic stress in tumor cells.…”

Section: Conceptual Cross-talkmentioning

confidence: 99%

Life and death partners: apoptosis, autophagy and the cross-talk between them

et al. 2009

View full text Add to dashboard Cite

It is not surprising that the demise of a cell is a complex well-controlled process. Apoptosis, the first genetically programmed death process identified, has been extensively studied and its contribution to the pathogenesis of disease well documented. Yet, apoptosis does not function alone to determine a cell's fate. More recently, autophagy, a process in which de novo-formed membrane-enclosed vesicles engulf and consume cellular components, has been shown to engage in a complex interplay with apoptosis. In some cellular settings, it can serve as a cell survival pathway, suppressing apoptosis, and in others, it can lead to death itself, either in collaboration with apoptosis or as a back-up mechanism when the former is defective. The molecular regulators of both pathways are inter-connected; numerous death stimuli are capable of activating either pathway, and both pathways share several genes that are critical for their respective execution. The cross-talk between apoptosis and autophagy is therefore quite complex, and sometimes contradictory, but surely critical to the overall fate of the cell. Furthermore, the crosstalk is a key factor in the outcome of death-related pathologies such as cancer, its development and treatment. Autophagy, a process long known to provide a survival advantage to cells undergoing nutrient deprivation or other stresses, has also been more recently linked to the actual death process itself. Thus apoptosis is not the sole means by which the cell can undergo a genetically programmed regulated process by which it undergoes self-elimination. Cell death can occur by several mechanisms and the phenotypic changes that accompany cell death can vary depending on the stimulus and cell setting. In any given death scenario, the cell decides which pathway to use, depending on the nature of the stimulus and the particulars of the cell environment. Furthermore, apoptosis and autophagy are not mutually exclusive pathways. They have been shown to act in synergy and also to counter each other. They share many of the same molecular regulators. In a clinical setting, one cannot predict the outcome of inhibition or activation of one death program without considering the effect on the other. This review will focus on the cross-talk between the autophagic and apoptotic pathways, with an analysis of how this may affect the clinical applications of death suppression/activation to cancer. The process of necrosis, the third means by which the cell can undergo a genetically programmed self-elimination, will not be discussed in detail. Although not intended to provide an exhaustive summary of the recent literature, the discussion will include salient experimental results as examples of the different facets of the apoptosis/autophagy interplay.An issue that has been raised and discussed in the literature is that in many cell settings, autophagy accompanies, rather than causes, cell death. 1 This argument is based on the fact that many studies that claim autophagic cell death prove that autophagy occurs, and that ...

show abstract

“…10 While the studies of Beclin 1 and UVRAG provide extensive evidence supporting autophagy as playing a role in the prevention of cancer, there are equal or greater amounts of evidence supporting autophagy's role in the promotion of cancer. [15][16][17] Thus, as a doubleedged sword, autophagy may contribute to both the promotion and prevention of cancer, which is dependent on the types, stages, and environments of cancer. Autophagy in early stage cancer may act as a tumor suppressor.…”

mentioning

confidence: 99%