Protective effect of autophagy in laser‐induced glioma cell death in vitro

Krmpot, Aleksandar J.; Janjetović, Kristina; Misirkić, Maja; Vučićević, Ljubica; Pantelić, Dejan; Vasiljević, Darko; Popadić, Dušan; Jelenković, Branislav; Trajkovič, Vladimir

doi:10.1002/lsm.20911

Cited by 15 publications

(11 citation statements)

References 58 publications

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“…Similar to tumor cells defense mechanisms, one can therefore hypothesize that the ER stress consequent to 2-DG treatment in tumor-associated EC may contribute to autophagy and promote cell survival (this study). While protective effects of autophagy were observed in the cancer cell compartment in both laser-induced cell death33 and in resveratrol-induced cytotoxicity in glioma cells,34 inhibition of autophagy was on the other hand found to potentiate antiangiogenic effects of sulforaphane in an EC model 35. Our study provides evidence supporting the latter assumption whereas 2-DG-mediated inhibition of autophagy was only observed in carcinogen-treated HBMEC (Figure 7B).…”

Section: Discussionsupporting

confidence: 67%

Low intracellular ATP levels exacerbate carcinogen-induced inflammatory stress response and inhibit in vitro tubulogenesis in human brain endothelial cells

Tahanian

Peiro²,

Annabi³

2011

JIR

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Solid tumor development requires angiogenesis and is correlated to the expression of inflammatory markers through cellular metabolic and energetic adaptation. While high glycolysis rates enable the cancer cell compartment to generate adenosine triphosphate (ATP), very little is known about the impact of low intracellular ATP concentrations within the vascular endothelial cell compartment, which is responsible for tumor angiogenesis. Here, we investigated the effect of 2-deoxy-D-glucose (2-DG), a glucose analog that inhibits glycolysis through intracellular ATP depletion, on human brain microvascular endothelial cell (HBMEC) angiogenic properties. While preformed capillaries remained unaffected, we found that in vitro tubulogenesis was dose-dependently decreased by 2-DG and that this correlated with reduced intracellular ATP levels. Procarcinogenic signaling was induced with phorbol 12-myristate 13-acetate (PMA) and found to trigger the proinflammatory marker cyclooxygenase-2 (COX-2) and endoplasmic reticulum (ER) stress marker GRP78 expression, whose inductions were potentiated when PMA was combined with 2-DG treatment. Inversely, PMA-induced matrix-metalloproteinase-9 (MMP-9) gene expression and protein secretion were abrogated in the presence of 2-DG, and this can be partially explained by reduced nuclear factor-κB signaling. Collectively, we provide evidence for an intracellular ATP requirement in order for tubulogenesis to occur, and we link increases in ER stress to inflammation. A better understanding of the metabolic adaptations of the vascular endothelial cells that mediate tumor vascularization will help the development of new drugs and therapies.

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Section: Discussionsupporting

confidence: 67%

Low intracellular ATP levels exacerbate carcinogen-induced inflammatory stress response and inhibit in vitro tubulogenesis in human brain endothelial cells

Tahanian

Peiro²,

Annabi³

2011

JIR

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“…The results of MTT and crystal violet assays were presented as % of the control values obtained from untreated cells. The cell viability was calculated as follows [11]. The % of dead cells (A sample A blank) (A control A blank) 100 = − − × .…”

Section: Cytotoxicity Assaysmentioning

confidence: 99%

Dichloroacetic Acid (DCA)-Induced Cytotoxicity in Human Breast Cancer Cells Accompanies Changes in Mitochondrial Membrane Permeability and Production of Reactive Oxygen Species

Al-Karakooly¹,

Kilaparty²,

Al-Anbaky³

et al. 2014

JCT

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Cancer cells utilize cytosolic glycolysis for their energy production even in the presence of adequate levels of oxygen (Warbug effect) due to mitochondrial defects. Dichloroacetic acid (DCA) shifts cytosolic glucose metabolism to aerobic oxidation by inhibiting mitochondrial pyruvate dehydrogenase kinase (PDK) and increasing pyruvate uptake. Therefore, DCA has potential in reversing the glycolytic metabolism defect in cancerous cells. DCA is also known to induce apoptosis in a number of cancer cell lines, the mechanism of which is not well understood. In this study, an attempt has been made to investigate the effects of DCA on aggressive human breast cancer (MCF-7) cells as compared with less aggressive mouse osteoblastic (MC3T3) cells. Cell cytotoxicity was determined by MTT, crystal violet and Trypan blue exclusion assays. Western blot was used to detect any changes in the expression of apoptotic markers. Flow cytometry was used to measure apoptotic and necrotic effects of DCA. Mitochondrial integrity was determined by change in mitochondrial membrane potential (Δψm), whereas oxidative damage was determined by production * Corresponding author. Z. Alkarakooly et al. 1235of reactive oxygen species (ROS). DCA caused a concentration-dependent cytotoxicity both in MCF-7 and MC3T3 cell lines. MCF-7 cells were most affected. Flow cytometry results showed a significantly higher apoptosis in MCF-7 even at lower concentrations of DCA. However, higher concentrations of DCA were necrotic. Western blotting showed an increased expression of Mn-SOD-1 upon DCA treatment. Further, DCA decreased Δψm and increased ROS production. The effects of DCA were more pronounced on MCF-7 cells as compared to MC3T3 cells. Our results suggest that DCA-induced cytotoxicity in cancerous cells is mediated via changes in Δψm and production of ROS.

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“…Protective autophagy helps tumor cells to survive in conditions with increased metabolic demands by mitigating damage and recovering normal functions and protecting the cell from death [ 11 ]. Autophagy is induced in human cancer cells in response to laser irradiation [ 12 ]. Autophagy inhibitors increase the cytotoxicity of laser irradiation at 532 nm in glioma cells [ 12 ], suggesting that autophagy protects tumor cells from laser-induced stress.…”

Section: Introductionmentioning

confidence: 99%

RelA-Mediated BECN1 Expression Is Required for Reactive Oxygen Species-Induced Autophagy in Oral Cancer Cells Exposed to Low-Power Laser Irradiation

Shu¹,

Chang²,

Wu³

et al. 2016

PLoS ONE

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Low-power laser irradiation (LPLI) is a non-invasive and safe method for cancer treatment that alters a variety of physiological processes in the cells. Autophagy can play either a cytoprotective role or a detrimental role in cancer cells exposed to stress. The detailed mechanisms of autophagy and its role on cytotoxicity in oral cancer cells exposed to LPLI remain unclear. In this study, we showed that LPLI at 810 nm with energy density 60 J/cm2 increased the number of microtubule associated protein 1 light chain 3 (MAP1LC3) puncta and increased autophagic flux in oral cancer cells. Moreover, reactive oxygen species (ROS) production was induced, which increased RelA transcriptional activity and beclin 1 (BECN1) expression in oral cancer cells irradiated with LPLI. Furthermore, ROS scavenger or knockdown of RelA diminished LPLI-induced BECN1 expression and MAP1LC3-II conversion. In addition, pharmacological and genetic ablation of autophagy significantly enhanced the effects of LPLI-induced apoptosis in oral cancer cells. These results suggest that autophagy may be a resistant mechanism for LPLI-induced apoptosis in oral cancer cells.

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Protective effect of autophagy in laser‐induced glioma cell death in vitro

Abstract: These data indicate that beclin-1-dependent induction of autophagy can protect glioma cells from laser-mediated cytotoxicity.

Cited by 15 publications

References 58 publications

Low intracellular ATP levels exacerbate carcinogen-induced inflammatory stress response and inhibit in vitro tubulogenesis in human brain endothelial cells

Low intracellular ATP levels exacerbate carcinogen-induced inflammatory stress response and inhibit in vitro tubulogenesis in human brain endothelial cells

Dichloroacetic Acid (DCA)-Induced Cytotoxicity in Human Breast Cancer Cells Accompanies Changes in Mitochondrial Membrane Permeability and Production of Reactive Oxygen Species

RelA-Mediated BECN1 Expression Is Required for Reactive Oxygen Species-Induced Autophagy in Oral Cancer Cells Exposed to Low-Power Laser Irradiation

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