Redox Regulation of Calcium Signaling in Cancer Cells by Ascorbic Acid Involving the Mitochondrial Electron Transport Chain

Мартинович, Г. Г.; Голубева, Е. Н.; Мартинович, И. В.; Черенкевич, С. Н.

doi:10.1155/2012/921653

Cited by 19 publications

(8 citation statements)

References 28 publications

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“…In addition to their metabolic and apoptotic roles, mitochondria also serve as a major hub of cellular Ca 2+ homeostasis. Indeed, mitochondrial Ca 2+ homeostasis is fundamental for a wide range of cellular activities, such as control of oxidative phosphorylation [98,99], modulation of cytosolic calcium signals [100], cell death [101], secretion [102,103] and reactive oxygen species (ROS) production in cancerous cells [104]. Intra-mitochondrial Ca 2+ controls energy metabolism by enhancing the rate of NADH production by modulating critical enzymes, such as those of the tricarboxylic acid (TCA) cycle and fatty acid oxidation [105,106], linking glycolysis to the TCA cycle [107] (Fig.…”

Section: Vdac1 As a Ca 2+ Transportermentioning

confidence: 99%

The mitochondrial voltage-dependent anion channel 1 in tumor cells

Shoshan‐Barmatz

Ben-Hail

Admoni

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

214

254

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VDAC1 is found at the crossroads of metabolic and survival pathways. VDAC1 controls metabolic cross-talk between mitochondria and the rest of the cell by allowing the influx and efflux of metabolites, ions, nucleotides, Ca2+ and more. The location of VDAC1 at the outer mitochondrial membrane also enables its interaction with proteins that mediate and regulate the integration of mitochondrial functions with cellular activities. As a transporter of metabolites, VDAC1 contributes to the metabolic phenotype of cancer cells. Indeed, this protein is over-expressed in many cancer types, and silencing of VDAC1 expression induces an inhibition of tumor development. At the same time, along with regulating cellular energy production and metabolism, VDAC1 is involved in the process of mitochondria-mediated apoptosis by mediating the release of apoptotic proteins and interacting with anti-apoptotic proteins. The engagement of VDAC1 in the release of apoptotic proteins located in the inter-membranal space involves VDAC1 oligomerization that mediates the release of cytochrome c and AIF to the cytosol, subsequently leading to apoptotic cell death. Apoptosis can also be regulated by VDAC1, serving as an anchor point for mitochondria-interacting proteins, such as hexokinase (HK), Bcl2 and Bcl-xL, some of which are also highly expressed in many cancers. By binding to VDAC1, HK provides both a metabolic benefit and apoptosis-suppressive capacity that offer the cell a proliferative advantage and increase its resistance to chemotherapy. Thus, these and other functions point to VDAC1 as an excellent target for impairing the re-programed metabolism of cancer cells and their ability to evade apoptosis. Here, we review current evidence pointing to the function of VDAC1 in cell life and death, and highlight these functions in relation to both cancer development and therapy. In addressing the recently solved 3D structures of VDAC1, this review will point to structure-function relationships of VDAC as critical for deciphering how this channel can perform such a variety of roles, all of which are important for cell life and death. Finally, this review will also provide insight into VDAC function in Ca2+ homeostasis, protection against oxidative stress, regulation of apoptosis and involvement in several diseases, as well as its role in the action of different drugs. We will discuss the use of VDAC1-based strategies to attack the altered metabolism and apoptosis of cancer cells. These strategies include specific siRNA able to impair energy and metabolic homeostasis, leading to arrested cancer cell growth and tumor development, as well VDAC1-based peptides that interact with anti-apoptotic proteins to induce apoptosis, thereby overcoming the resistance of cancer cell to chemotherapy. Finally, small molecules targeting VDAC1 can induce apoptosis. VDAC1 can thus be considered as standing at the crossroads between mitochondrial metabolite transport and apoptosis and hence represents an emerging cancer drug target. This article is part of a Special ...

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Section: Vdac1 As a Ca 2+ Transportermentioning

confidence: 99%

The mitochondrial voltage-dependent anion channel 1 in tumor cells

Shoshan‐Barmatz

Ben-Hail

Admoni

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

214

254

View full text Add to dashboard Cite

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“…A possesses both pro-oxidant and anti-oxidant properties (42)(43)(44)(45)(46)(47)(48)(49)(50). Although the preventive anti-cancer effect of A results from its anti-oxidant properties (42), previous in vitro studies and mouse models have demonstrated that A is able to inhibit cell proliferation in various types of cancer due to its ability to induce the production of H 2 O 2 (43-49) without being toxic to non-cancerous cells (43,50).…”

Section: Discussionmentioning

confidence: 99%

Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro

et al. 2016

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Abstract.Ascorbic acid (A) has been demonstrated to exhibit anti-cancer activity in association with chemotherapeutic agents. Potassium (K) is a regulator of cellular proliferation. In the present study, the biological effects of A and K bicarbonate, alone or in combination (A+K), on breast cancer cell lines were evaluated. The survival of cancer cells was determined by sulforhodamine B cell proliferation assay, while analysis of the cell cycle distribution was conducted via fluorescence-activated cell sorting. In addition, the expression of signaling proteins was analyzed upon treatment. The results indicated that there was a heterogeneous response of the different cell lines to A and K, and the best effects were achieved by A+K and A treatment. The interaction between A+K indicated an additive or synergistic effect. In addition, A+K increased the percentage of cells in the sub-G1 phase of the cell cycle, and was the most effective treatment in activating the degradation of poly(adenosine diphosphate-ribose) polymerase-1. In the breast cancer cell line MCF-7, A+K induced the appearance of the 18 kDa isoform of B-cell lymphoma-2-associated X protein (Bax), which is a more potent inducer of apoptosis than the full-length Bax-p21. The effects of A and K on the phosphorylation of extracellular signal-regulated kinase (ERK)1 and ERK2 were heterogeneous. In addition, treatment with K, A and A+K inhibited the expression of nuclear factor-κB. Overall, the results of the present study indicated that K potentiated the anti-tumoral effects of A in breast cancer cells in vitro.

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“…Hence, elevated levels of reactive oxygen species (ROS) due to hydrogen peroxide formed, causes the toxicity to cancer cells. Induction of apoptosis, 27 autophagy, 26 impairment of mitochondrial structure, 28 and Ca 2+ release from mitochondria, 29 was concluded to be a consequence of increase in ROS production, upon exposure to vitamin C in high doses.…”

Section: Introductionmentioning

confidence: 99%

Effect of vitamin C and E supplementation on human gastrointestinal tract tissues and cells: Raman spectroscopy and imaging studies

Miazek

Beton

Brożek-Płuska

2021

Preprint

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Cancer of gastrointestinal tract, such as colorectal cancer (CRC) and gastric cancer (GC), are common types of cancer globally and their origin can be linked to oxidative stress conditions. Commonly available antioxidants, such as vitamins C and E, are widely considered as potential anti-cancer agents. Raman spectra have great potential in the biochemical characterization of matter based on the fact that each molecule has its own unique vibrational properties. Raman spectroscopy allows to precisely characterized cell substructures (nucleus, mitochondria, cytoplasm, cell membrane) and components (proteins, lipids, nucleic acids).The paper presents the application of the Raman spectroscopy technique for the analysis of tissue samples and cells of the human colon and stomach. The main goal of this study is to show the differences between healthy and cancerous tissues from the human digestive tract and human normal and cancer colon and gastric cell lines. The paper presents the spectroscopic characterization of normal colon cells - CCD-18 Co in physiological and oxidative conditions and effect of oxidative injury of normal colon cells upon supplementation with vitamin C at various concentrations based on Raman spectra. The obtained results were related to the Raman spectra recorded for human colon cancer cells - Caco-2. In addition, the effect of the antioxidant in the form of vitamin E on gastric cancer cells - HTB-135 is presented and compared with normal gastric cells - CRL-7869. All measured gastric samples were biochemically and structurally characterized by means of Raman spectroscopy and imaging. Statistically assisted analysis has shown that normal, ROS injured and cancerous human gastrointestinal cells can be distinguished based on their unique vibrational properties.The conducted research based on Raman spectra proved that antioxidants in the form of vitamin C and E exhibit anti-cancer properties. In consequence, conducted studies proved that label-free Raman spectroscopy may play an important role in clinical diagnostics differentiation of human normal and cancerous gastrointestinal tissues and may be a source of intraoperative information supporting histopathological analysis.

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Redox Regulation of Calcium Signaling in Cancer Cells by Ascorbic Acid Involving the Mitochondrial Electron Transport Chain

Cited by 19 publications

References 28 publications

The mitochondrial voltage-dependent anion channel 1 in tumor cells

The mitochondrial voltage-dependent anion channel 1 in tumor cells

Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro

Effect of vitamin C and E supplementation on human gastrointestinal tract tissues and cells: Raman spectroscopy and imaging studies

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