The effect of 3-bromopyruvate on human colorectal cancer cells is dependent on glucose concentration but not hexokinase II expression

Ho, Nelson; Morrison, Jodi; Silva, Andreza; Coomber, Brenda L.

doi:10.1042/bsr20150267

Cited by 20 publications

(9 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To explore butyrate uptake, LDH releasing assay was performed by 3-BrPA, which is MCT1 selective substrate and lead to cell death [ 20 , 21 ]. Cyclosporine treatment increased LDH release in supernatant, however, it was canceled by CHC administration ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…To determine the transport by MCT1 in Caco-2 cell transport, 3-bromopyruvate(3-BrPA)(Sigma-Aldrich), is a selective MCT1 substrate, induce to cell death by inhibiting GAPDH after transported into cell [ 20 , 21 ]. Caco-2 cells were seeding to 24 well plate, and cultured in DMEM supplemented with 10% FBS, and with the medium being replaced every other day for 14–21 days.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Cyclosporine protects from intestinal epithelial injury by modulating butyrate uptake via upregulation of membrane monocarboxylate transporter 1 levels

Ota

Sakuraba

Hiraga

et al. 2020

Biochemistry and Biophysics Reports

View full text Add to dashboard Cite

Background and aims A relationship between treatment outcomes and intestinal microbiota in patients with inflammatory bowel diseases has been demonstrated. Cyclosporine treatment leads to rapid improvement in severe ulcerative colitis. We hypothesized that the potent effects of cyclosporine would be exerted through relationships between intestinal epithelial cells (IECs) and the host microbiota. The present study was designed to elucidate the effects of cyclosporine on monocarboxylate transporter 1 (MCT1) regulation and butyrate uptake by IECs. Methods Colitis was induced in C57BL6 mice via the administration of 4% dextran sulfate sodium in drinking water, following which body weights, colon lengths, and histological scores were evaluated. To examine the role of butyrate in the protective effects of cyclosporine, MCT1 inhibitor and an antibiotic cocktail was administered and tributyrin (TB; a prodrug of butyrate) was supplemented; MCT1 protein expression and acetylated histone 3 (AcH3) signals in IECs, as well as the MCT1-membrane fraction of Caco-2 cells, were evaluated. To explore butyrate uptake, as s butyrate derivatives, 3-bromopyruvic acid (3-BrPA) and 1-pyrenebutyric acid were used. Results Treatment with cyclosporine inhibited body weight loss and colon length shortening. However, treatment with MCT1 inhibitor and the antibiotic cocktail negated the efficacy of cyclosporine, whereas TB supplementation restored its protective effect. Furthermore, cyclosporine upregulated MCT1 expression in the membrane and the AcH3 signal in IECs, while also inducing higher anti-inflammatory cytokine production compared to that in the vehicle-treated mice. The transcription level of MCT1 mRNA in IECs and Caco-2 cells did not increase with cyclosporine treatment; however, cyclosporine treatment increased membrane MCT1 expression in these cells and uptake of butyrate derivative. Conclusion Cyclosporine treatment modulates butyrate uptake via the post-transcriptional upregulation of membrane MCT1 levels in IECs.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Cyclosporine protects from intestinal epithelial injury by modulating butyrate uptake via upregulation of membrane monocarboxylate transporter 1 levels

Ota

Sakuraba

Hiraga

et al. 2020

Biochemistry and Biophysics Reports

View full text Add to dashboard Cite

show abstract

“…3-Bromopyruvate (3-BP) is a Potent anticancer alkylating agent which exerts its anti-cancer influence via different molecules and pathways, including inhibition of key glycolysis enzymes (hexokinase II and lactate dehydrogenase), inhibition of mitochondrial oxidative phosphorylation, angiogenesis, and energy production in cancer cells. 3-Bromopyruvate (3-BP) also induces cancer cell death through hydrogen peroxide generation (oxidative stress effect) (Ho et al 2016;Schaefer et al 2012). 3-BP has been shown to have potent synergistic effects with various anti-cancer drugs in vitro and in vivo (Chong et al 2017).…”

Section: Discussionmentioning

confidence: 99%

3-Bromopyruvate potentiates TRAIL-induced apoptosis in human colon cancer cells through a reactive oxygen species- and caspase-dependent mitochondrial pathway

Abbaszadeh

Valizadeh

Mahdavinia

et al. 2019

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising anticancer cytokine with minimal toxicity towards normal cells. Nevertheless, most primary cancers are often intrinsically TRAIL-resistant or can acquire resistance after TRAIL therapy. This study aimed to investigate the inhibitory effect of co-treatment of 3-bromopyruvate (3-BP) as a potent anticancer agent with TRAIL on colon cancer cells (HT-29). The results of present study indicated that combined treatment with 3-BP and TRAIL inhibited the proliferation of HT-29 cells to a greater extent (88.4%) compared with 3-BP (54%) or TRAIL (11%) treatment alone. In contrast, the combination of 3-BP and TRAIL had no significant inhibitory effect on the proliferation of normal cells (HEK-293) (8.4%). At a cellular mechanistic level, the present study showed that 3-BP sensitized human colon cancer cells to TRAIL-induced apoptosis via reactive oxygen species generation, upregulation of Bax, downregulation of Bcl-2 and survivin, release of cytochrome c into the cytosol, and activation of caspase-3. In normal cells, 3-BP, TRAIL, or combination of both had no significant effect on the reactive oxygen species levels, release of cytochrome c, and caspase-3 activity. Therefore, the combination of 3-BP and TRAIL can be a promising therapeutic strategy for treatment of colon cancer.

show abstract

“…Again, HL60 and THP1 proved to be more competent in monocarboxylates uptake than HEL, since HL60 and THP1 showed a cell death upon BPA exposure 10 fold higher than without BPA, with or without VEGF (Figure 6B ). In addition, BPA is more death effective in cells that have high glucose demands, namely cancer cells that proliferate more [ 61 ]. The cell death profile was also different between cell lines, as it is described for BPA in other cancer models [ 62 ]: HL60 and THP1 showed double PI and annexin V positive cells, consistent with late apoptosis or necroptosis, whereas HEL cells died mainly through necrosis exhibited by the high PI positivity (Figure 6A ).…”

Section: Discussionmentioning

confidence: 99%

Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cells

et al. 2017

View full text Add to dashboard Cite

Dysregulation of glucose/lactate dynamics plays a role in cancer progression, and MCTs are key elements in metabolic remodeling. VEGF is a relevant growth factor in the maintenance of bone marrow microenvironment and it is also important in hematological diseases.Our aim was to investigate the role of VEGF in the metabolic adaptation of Acute myeloid leukemia (AML) cells by evaluating the metabolic profiles and cell features according to the AML lineage and testing lactate as a metabolic coin.Our in vitro results showed that AML promyelocytic (HL60) and monocytic (THP1) (but not erythroid- HEL) lineages are well adapted to VEGF and lactate rich environment. Their metabolic adaptation relies on high rates of glycolysis to generate intermediates for PPP to support cell proliferation, and on the consumption of glycolysis-generated lactate to supply biomass and energy production. VEGF orchestrates this metabolic network by regulating MCT1 expression. Bromopyruvic acid (BPA) was proven to be an effective cytotoxic in AML, possibly transported by MCT1.Our study reinforces that targeting metabolism can be a good strategy to fight cancer. MCT1 expression at the time of diagnosis can assist on the identification of AML patients that will benefit from BPA therapy. Additionally, MCT1 can be used in targeted delivery of conventional cytotoxic drugs.

show abstract

The effect of 3-bromopyruvate on human colorectal cancer cells is dependent on glucose concentration but not hexokinase II expression

Abstract: Colorectal cancer cells respond to 3BP via phosphorylation of AKT at residue Thr-308. The availability of glucose in culturing media plays a crucial role in 3BP sensitivity, although independently of HKII expression.

Cited by 20 publications

References 59 publications

Cyclosporine protects from intestinal epithelial injury by modulating butyrate uptake via upregulation of membrane monocarboxylate transporter 1 levels

Cyclosporine protects from intestinal epithelial injury by modulating butyrate uptake via upregulation of membrane monocarboxylate transporter 1 levels

3-Bromopyruvate potentiates TRAIL-induced apoptosis in human colon cancer cells through a reactive oxygen species- and caspase-dependent mitochondrial pathway

Monocarboxylate transporter 1 (MCT1), a tool to stratify acute myeloid leukemia (AML) patients and a vehicle to kill cancer cells

Contact Info

Product

Resources

About