Effect of 3-bromopyruvate acid on the redox equilibrium in non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells

Abstract

Novel approaches to cancer chemotherapy employ metabolic differences between normal and tumor cells, including the high dependence of cancer cells on glycolysis ("Warburg effect"). 3-Bromopyruvate (3-BP), inhibitor of glycolysis, belongs to anticancer drugs basing on this principle. 3-BP was tested for its capacity to kill human non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells. We found that 3-BP was more toxic for MDA-MB-231 cells than for MCF-7 cells. In both cell lines, a statistically significant decrease of ATP and glutathione was observed in a time- and 3-BP concentration-dependent manner. Transient increases in the level of reactive oxygen species and reactive oxygen species was observed, more pronounced in MCF-7 cells, followed by a decreasing tendency. Activities of glutathione peroxidase, glutathione reductase (GR) and glutathione S-transferase (GST) decreased in 3-BP treated MDA-MB-231 cells. For MCF-7 cells decreases of GR and GST activities were noted only at the highest concentration of 3-BP.These results point to induction of oxidative stress by 3-BP via depletion of antioxidants and inactivation of antioxidant enzymes, more pronounced in MDA-MB-231 cells, more sensitive to 3-BP.

Allele-specific interaction between glutathione peroxidase 1 and manganese superoxide dismutase affects the levels of Bcl-2, Sirt3 and E-cadherin

“…Again, the E-cadherin result is [55] consistent to that previously reported by Liu et al [35] while the reduction in Bcl-2 is contrary to what has been reported when MnSOD was expressed in lung carcinoma cells [56]. In all cases, differences due to the expression of distinct MnSOD alleles were minimal or not evident.…”

Epigenetically regulated Fibronectin leucine rich transmembrane protein 2 (FLRT2) shows tumor suppressor activity in breast cancer cells

“…5A). To observe the migration of cancer cells that overexpresses FLRT2, MDA-MB-231 cells were chosen instead of MCF-7 because the latter are known to be unsuitable for migration assays owing to their low migratory ability 35 . FLRT2-overexpressing cells showed a slight decrease in migration compared to control cells (Fig.…”

Mitochondrial VDAC1: A Key Gatekeeper as Potential Therapeutic Target

“…Clotrimazole has been shown to disrupt HK-VDAC1 association, and recently was reported to inhibit human breast cancer cell proliferation, viability and glycolysis by altering the rates of glucose uptake, mitochondrial activity and ATP generation (Furtado et al, 2012). Another potential anti-cancer drug, 3-bromopyruvic acid (3-BP), is an alkylating agent that is effective in inhibiting glycolysis in aggressive liver tumor cells by disrupting the HK-VDAC interaction (Gong et al, 2014), and inhibiting proliferation in a human breast cancer MCF-7 cell line by down-regulation of Bcl-2 (Liu et al, 2009; Kwiatkowska et al, 2016). In an animal model, 3-BP eradicated advanced stage, positron emission tomography (PET) positive hepatocellular carcinomas without apparent harm to the animals (Ko et al, 2004).…”

“…In an animal model, 3-BP eradicated advanced stage, positron emission tomography (PET) positive hepatocellular carcinomas without apparent harm to the animals (Ko et al, 2004). Recently 3-BP has also been shown to be an activator of oxidative stress by depleting antioxidants and inactivating antioxidant enzymes (Kwiatkowska et al, 2016). Another promising cancer fighting agent, jasmonate, derived from a plant stress hormone, has also been shown to act directly on mitochondria of cancer cells by detaching HK from the OMM and inducing cell death via mPTP opening (Rotem et al, 2005).…”