Copper compound induces autophagy and apoptosis of glioma cells by reactive oxygen species and jnk activation

Trejo-Solís, Cristina; Jiménez-Farfán, Dolores; Rodrı́guez-Enrı́quez, Sara; Fernández-Valverde, Francisca; Cruz-Salgado, Arturo; Ruíz-Azuara, Lena; Sotelo, Julio

doi:10.1186/1471-2407-12-156

Cited by 118 publications

(72 citation statements)

References 52 publications

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“…Similar observations were reported for paraquat (PQ) (1, 1′-dimethyl-4,4′-bipyridinium dichloride), a widely used herbicide, which was found to induce autophagy in the beginning while cells eventually died through apoptosis [36]. Several compounds have also been reported for simultaneous induction of autophagy and apoptosis in cancer cells [38,39,40,41]. In the past decade, it has become increasingly evident that massive ROS generation modulates autophagic pathways [42] contributing to cancer initiation and progression [30,43,44,45].…”

Section: Discussionsupporting

confidence: 69%

Autophagy Inhibition Enhances the Mitochondrial-Mediated Apoptosis Induced by Mangrove (Avicennia marina) Extract in Human Breast Cancer Cells

Esau

Sagar

Bajic

et al. 2015

EJMP

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Section: Discussionsupporting

confidence: 69%

Autophagy Inhibition Enhances the Mitochondrial-Mediated Apoptosis Induced by Mangrove (Avicennia marina) Extract in Human Breast Cancer Cells

Esau

Sagar

Bajic

et al. 2015

EJMP

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“…3; see also has not been previously reported in photosynthetic organisms, although in mammalian cancer cells, copper complexes appear to induce oxidative stress, which in turn triggers autophagy (63,64). Unlike the effect of Ni 2ϩ , copper, or cobalt, no significant effect of Cd 2ϩ or Hg 2ϩ ions, even at high concentrations (150 M and 2 M, respectively), on ATG8 was observed ( Fig.…”

Section: Discussionmentioning

confidence: 65%

Activation of Autophagy by Metals in Chlamydomonas reinhardtii

et al. 2015

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Autophagy is an intracellular self-degradation pathway by which eukaryotic cells recycle their own material in response to specific stress conditions. Exposure to high concentrations of metals causes cell damage, although the effect of metal stress on autophagy has not been explored in photosynthetic organisms. In this study, we investigated the effect of metal excess on autophagy in the model unicellular green alga Chlamydomonas reinhardtii. We show in cells treated with nickel an upregulation of ATG8 that is independent of CRR1, a global regulator of copper signaling in Chlamydomonas. A similar effect on ATG8 was observed with copper and cobalt but not with cadmium or mercury ions. Transcriptome sequencing data revealed an increase in the abundance of the protein degradation machinery, including that responsible for autophagy, and a substantial overlap of that increased abundance with the hydrogen peroxide response in cells treated with nickel ions. Thus, our results indicate that metal stress triggers autophagy in Chlamydomonas and suggest that excess nickel may cause oxidative damage, which in turn activates degradative pathways, including autophagy, to clear impaired components and recover cellular homeostasis. Eukaryotic cells are able to degrade and recycle their own material when they are exposed to nutrient starvation or other adverse conditions through a catabolic pathway known as macroautophagy or autophagy. This process is characterized by the formation of double-membrane vesicles termed autophagosomes that engulf and deliver cytosolic components to the vacuole/lysosome for degradation (1-4). The primary function of autophagy is to recycle cytoplasmic material as well as to clear damaged organelles or toxic cellular components generated during stress in order to maintain cellular homeostasis. In higher eukaryotes, autophagy has also been implicated in cell differentiation, development and cell death, and several human pathologies, such as cancer and neurodegenerative diseases (5, 6).Autophagy is mediated by highly conserved autophagy-related (ATG) genes, which have been described in organisms ranging from yeasts to mammals. Some ATG proteins are required for the formation of the autophagosome and constitute the core autophagy machinery (4,7,8). This group of proteins includes the ATG8 and ATG12 ubiquitin-like systems required for vesicle expansion. The ATG8 protein has been widely used to monitor autophagy in many systems (9) because, unlike other ATG proteins, this protein firmly binds to the autophagosome membrane through a covalent bond to phosphatidylethanolamine (PE). Most of the core ATG proteins are conserved in land plants (10-12) and in evolutionarily distant algae, including freshwater species, such as the model green alga Chlamydomonas reinhardtii (herein referred to as Chlamydomonas) (13) and marine species (14). Our current knowledge about autophagy in algae is still limited compared to our knowledge about autophagy in other eukaryotes, but recent studies, mainly performed in Chlamydomon...

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“…Autophagy is a type of programmed cell death and it is an important process that is involved in various human pathologies. Previous studies suggest that autophagy is important in the regulation of cancer development and progression and also in determining the response of tumor cells to anticancer therapy (11)(12)(13)(14). Several cell signaling pathways are implicated in regulating autophagy, including the phosphatidyl inositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway (15,16).…”

Section: Introductionmentioning

confidence: 99%

Role of autophagy in the ω-3 long chain polyunsaturated fatty acid-induced death of lung cancer A549 cells

Yao

Wang

et al. 2015

Oncology Letters

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Abstract. The present study identified that ω-3 long chain polyunsaturated fatty acids (ω-3 PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) demonstrate anti-proliferative effects in lung cancer A549 cells. MTS and cytotoxicity assays were conducted to confirm that ω-3 PUFAs induced cell death. Autophagy-associated gene and signaling pathways were also detected. Microtubule-associated protein light chain 3 (LC3) expression was found to be increased subsequent to treatment with DHA and EPA, and the expression of LC3-II was particularly increased. mRFP-GFP-LC3 fluorescence staining and p62 expression levels were used to detect autophagic flux. The present results indicate that DHA and EPA block autophagic flux, suggesting autophagosome accumulation. Subsequent to treatment with DHA and EPA, which interfered with autophagosomes, the expression of Beclin 1 was significantly decreased, while the expression of phosphorylated Akt and phosphorylated mammalian target of rapamycin was significantly increased. Therefore, DHA and EPA exert anti-proliferative effects by inhibiting autophagy in A549 cells, which highlights the potential of DHA and EPA for use in the prevention or treatment of lung cancer. IntroductionLung cancer is the leading cause of cancer-associated mortality worldwide (1), and the five-year survival rate remains extremely poor (2). Overall, ~75-85% of lung cancers cases are non-small cell lung cancer (NSCLC), which includes squamous cell carcinoma, adenocarcinoma and large cell carcinoma. The treatment of lung cancer involves the use of medical therapies such as surgery, radiation, chemotherapy and palliative care (3) in an attempt to successfully treat or reduce the adverse impact of malignant neoplasms originating in lung tissue. Chemotherapeutic agents are the main treatment measures for NSCLC, but the side-effects are usually difficult to tolerate (4).Fish oils are an excellent source of long-chain ω-3 polyunsaturated fatty acids (ω-3 PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Fish oil supplements are increasingly recognized by clinical studies to be useful for the treatment of a variety of human afflictions, including cancer (5). Numerous studies reveal evidence for the capability of ω-3 PUFAs to decrease proliferation, exert a pro-apoptotic effect and inhibit angiogenesis in several in vitro models of colon cancer (6-9).A previous study indicated that DHA and EPA inhibit the proliferation of A549 cells and induce apoptosis, with autophagy also being observed under transmission electron microscopy (10). Autophagy is a type of programmed cell death and it is an important process that is involved in various human pathologies. Previous studies suggest that autophagy is important in the regulation of cancer development and progression and also in determining the response of tumor cells to anticancer therapy (11)(12)(13)(14). Several cell signaling pathways are implicated in regulating autophagy, including the phosphatidyl inositol 3-kinase (PI3K)/Akt/...

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Copper compound induces autophagy and apoptosis of glioma cells by reactive oxygen species and jnk activation

Cited by 118 publications

References 52 publications

Autophagy Inhibition Enhances the Mitochondrial-Mediated Apoptosis Induced by Mangrove (Avicennia marina) Extract in Human Breast Cancer Cells

Autophagy Inhibition Enhances the Mitochondrial-Mediated Apoptosis Induced by Mangrove (Avicennia marina) Extract in Human Breast Cancer Cells

Activation of Autophagy by Metals in Chlamydomonas reinhardtii

Role of autophagy in the ω-3 long chain polyunsaturated fatty acid-induced death of lung cancer A549 cells

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