Investigation on the mechanism of dichloroacetate (DCA) induced apoptosis in breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14637-e14637
Author(s):  
L. Ko ◽  
J. Allalunis-Turner
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Glucose Metabolism ◽  
Cell Lines ◽  
Pyruvate Dehydrogenase ◽  
Breast Cancer Cell Lines ◽  
Mitochondrial Activity ◽  
Rt Pcr ◽  
Induced Apoptosis ◽  
Mcf 7

e14637 Background: DCA is a generic, orally available, small molecule metabolic modulator that has an established history in the treatment of mitochondrial diseases and lactic acidosis. DCA inhibits pyruvate dehydrogenase kinase (PDK), an inhibitor of pyruvate dehydrogenase, a key enzyme in glucose metabolism. DCA preferentially shifts glucose metabolism in cancer cells from glycolysis to glucose oxidation, reversing the unique aerobic glycolysis found in solid tumors. DCA induced apoptosis in cancer cells as evidenced by the efflux of cytochrome c and apoptosis-inducing factor from the mitochondria. Recent studies suggested apoptosis induction by DCA in glioblastoma, endometrial, prostate, and non-small cell lung cancers. In this study we attempt to establish a link between DCA and apoptosis in breast cancer cell lines. Methods: Six breast cancer cell lines were investigated (BT474, MCF-7, MDA-MB231, MDA- MB468, SKBR3, T47D). Quantitative real-time polymerase chain reaction (RT-PCR) was performed using Taqman probes to identify increased DNA templates of PDK isoforms 1–4, using DCA concentrations from 0 to 20mM. Western blots were performed to identify increased expression of PDK isoforms and correlate findings with Taqman. MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)- 2-(4-sulfophenyl)-2H-tetrazolium) assays were performed to measure decreased mitochondrial activity and cytotoxicity. Flow cytometry using annexin V and propidium iodide was performed to measure apoptosis and cell death. Results: RT-PCR showed increased DNA expression of all PDK isoforms in MDA-MB231 cells after DCA treatment. The effect was most pronounced at 10mM concentration. 10mM of DCA also increased DNA expression of all PDK isoforms in MCF-7 cells, and PDK1 in T47D cells. MTS assays showed increased cell kill and decreased mitochondrial activity in all six cell lines, with IC50 ranging between 20mM and 30 mM. Flow cytometry showed increased apoptosis induced by DCA at IC50 for BT474 and MCF-7 cell lines. Conclusions: Apoptosis appears to play a role in the mechanism of DCA in breast cancer, with increased PDK isoform expressions, cytotoxicity and decreased mitochondrial activity. Data from flow cytometry suggested DCA-induced apoptosis in two cell lines. No significant financial relationships to disclose.

scholarly journals Low Intensity Ultrasound Induced Apoptosis in MCF-7 Breast Cancer Cell Lines

2017 ◽  
Vol 46 (4) ◽  
pp. 575-581 ◽  
Author(s):  
Siti P.M. Bohari ◽  
Hamidreza Aboulkheyr E.S. ◽  
Nur S. Johan ◽  
Nursyuhada F. Zainudin
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Low Intensity ◽  
Low Intensity Ultrasound ◽  
Induced Apoptosis ◽  
Mcf 7

Validation of real-time RT-PCR for analysis of human breast cancer cell lines resistant or sensitive to treatment with antiestrogens.

2003 ◽  
pp. 409-418 ◽  
Author(s):  
P de Cremoux ◽  
C Tran-Perennou ◽  
B L Brockdorff ◽  
E Boudou ◽  
N Br√ºnner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Real Time ◽  
Cell Lines ◽  
Model System ◽  
Model Systems ◽  
Breast Cancer Cell Lines ◽  
Antiestrogen Resistance ◽  
Human Breast ◽  
Rt Pcr ◽  
Mcf 7

Using a quantitative real-time RT-PCR technique we have compared the expression of a number of genes in two different human breast cancer model systems for development of acquired resistance to antiestrogens. The model system developed at the Danish Cancer Society comprises the cell lines MCF-7, MCF-7/TAMR-1, MCF-7/182R-6 and MCF-7/182R-7, and the model system developed at the Lombardi Cancer Research Center consists of the cell lines MCF-7/LCC1, MCF-7/LCC2 and MCF-7/LCC9. The findings on the well-known parameters estrogen receptor (ER)alpha, progesterone receptor (PR) and epidermal growth factor receptor (EGFR) are in good agreement with previous reports, thus documenting the usefulness of the real-time RT-PCR technique for multiparametric RNA analysis. The gene expression levels in the two model systems were found to be quite similar in relation to ERalpha, AIB1 (amplified in breast cancer-1), breast cancer antiestrogen resistance gene 1 (BCAR1) and ErbB-2 mRNA expression, whereas significant differences were observed on the expression of ERbeta, multidrug resistance gene 1 (MDR1), PR and EGFR. Furthermore, the presented data suggest that ERbeta, AIB1, BCAR1, CYP19 and MDR1 are unlikely to be causally involved in development of antiestrogen resistance in these breast cancer cell lines.

scholarly journals Jujuboside B Inhibits the Proliferation of Breast Cancer Cell Lines by Inducing Apoptosis and Autophagy

2021 ◽  
Vol 12 ◽  
Author(s):  
Lin Guo ◽  
Yupei Liang ◽  
Shiwen Wang ◽  
Lihui Li ◽  
Lili Cai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Biologically Active ◽  
Breast Cancer Cell Lines ◽  
Induced Apoptosis ◽  
Mcf 7

Jujuboside B (JB) is one of the main biologically active ingredients extracted from Zizyphi Spinosi Semen (ZSS), a widely used traditional Chinese medicine for treating insomnia and anxiety. Breast cancer is the most common cancer and the second leading cause of cancer-related death in women worldwide. The purpose of this study was to examine whether JB could prevent breast cancer and its underlying mechanism. First, we reported that JB induced apoptosis and autophagy in MDA-MB-231 and MCF-7 human breast cancer cell lines. Further mechanistic studies have revealed that JB-induced apoptosis was mediated by NOXA in both two cell lines. Moreover, the AMPK signaling pathway plays an important role in JB-induced autophagy in MCF-7. To confirm the anti-breast cancer effect of JB, the interaction of JB-induced apoptosis and autophagy was investigated by both pharmacological and genetic approaches. Results indicated that autophagy played a pro-survival role in attenuating apoptosis. Further in vivo study showed that JB significantly suppressed the growth of MDA-MB-231 and MCF-7 xenografts. In conclusion, our findings indicate that JB exerts its anti-breast cancer effect in association with the induction of apoptosis and autophagy.

scholarly journals Pitaya Extracts Induce Growth Inhibition and Proapoptotic Effects on Human Cell Lines of Breast Cancer via Downregulation of Estrogen Receptor Gene Expression

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Deborah de Almeida Bauer Guimarães ◽  
Danielle dos Santos Bonfim De Castro ◽  
Felipe Leite de Oliveira ◽  
Eduardo Matos Nogueira ◽  
Marco Antônio Mota da Silva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Cycle ◽  
Cell Line ◽  
Cell Lines ◽  
Receptor Gene ◽  
Breast Cancer Cell Lines ◽  
Cell Line Cell ◽  
Induced Apoptosis ◽  
Mcf 7

Breast cancer is one of the most prevalent cancers in the world and is also the leading cause of cancer death in women. The use of bioactive compounds of functional foods contributes to reduce the risk of chronic diseases, such as cancer and vascular disorders. In this study, we evaluated the antioxidant potential and the influence of pitaya extract (PE) on cell viability, colony formation, cell cycle, apoptosis, and expression of BRCA1, BRCA2, PRAB, and Erα in breast cancer cell lines (MCF-7 and MDA-MB-435). PE showed high antioxidant activity and high values of anthocyanins (74.65 ± 2.18). We observed a selective decrease in cell proliferation caused by PE in MCF-7 (ER+) cell line. Cell cycle analysis revealed that PE induced an increase in G0/G1 phase followed by a decrease in G2/M phase. Also, PE induced apoptosis in MCF-7 (ER+) cell line and suppressed BRCA1, BRCA2, PRAB, and Erα gene expression. Finally, we also demonstrate that no effect was observed with MDA-MB-435 cells (ER−) after PE treatment. Taken together, the present study suggests that pitaya may have a protective effect against breast cancer.

scholarly journals Optimized Polyethylene Glycolylated Polymer–Lipid Hybrid Nanoparticles as a Potential Breast Cancer Treatment

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 666
Author(s):  
Salam Massadeh ◽  
Mustafa E Omer ◽  
Asmaa Alterawi ◽  
Rizwan Ali ◽  
Fayez H Alanazi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Particle Size ◽  
Zeta Potential ◽  
Cell Lines ◽  
Entrapment Efficiency ◽  
Hybrid Nanoparticles ◽  
Breast Cancer Cell Lines ◽  
Size Uniformity ◽  
Mcf 7

Purpose: The aim of this work is to optimize a polyethylene glycolated (PEGylated) polymer–lipid hybrid nanoparticulate system for the delivery of anastrozole (ANS) to enhance its biopharmaceutical attributes and overall efficacy. Methods: ANS loaded PEGylated polymer–lipid hybrid nanoparticles (PLNPs) were prepared by a direct emulsification solvent evaporation method. The physical incorporation of PEG was optimized using variable ratios. The produced particles were evaluated to discern their particle size and shape, zeta-potential, entrapment efficiency, and physical stability. The drug-release profiles were studied, and the kinetic model was analyzed. The anticancer activity of the ANS PLNPs on estrogen-positive breast cancer cell lines was determined using flow cytometry. Results: The prepared ANS-PLNPs showed particle sizes in the range of 193.6 ± 2.9 to 218.2 ± 1.9 nm, with good particle size uniformity (i.e., poly-dispersity index of around 0.1). Furthermore, they exhibited relatively low zeta-potential values ranging from −0.50 ± 0.52 to 6.01 ± 4.74. The transmission electron microscopy images showed spherical shape of ANS-PLNPs and the compliance with the sizes were revealed by light scattering. The differential scanning calorimetry DSC patterns of the ANS PLNPs revealed a disappearance of the characteristic sharp melting peak of pure ANS, supporting the incorporation of the drug into the polymeric matrices of the nanoparticles. Flow cytometry showed the apoptosis of MCF-7 cell lines in the presence of ANS-PLNPs. Conclusion: PEGylated polymeric nanoparticles presented a stable encapsulated system with which to incorporate an anticancer drug (ANS) with a high percentage of entrapment efficiency (around 80%), good size uniformity, and induction of apoptosis in MCF-7 cells.

Cytotoxic activity and anti-cancer potential of Ontario grown onion extracts against breast cancer cell lines

2018 ◽  
Vol 8 (3) ◽  
pp. 159 ◽  
Author(s):  
Meghan Fragis ◽  
Abdulmonem I. Murayyan ◽  
Suresh Neethirajan
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Cytotoxic Activities ◽  
Cancer Line ◽  
Mcf 7

Background: Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths among Canadian women. Cancer management through changes in lifestyle, such as increased intake of foods rich in dietary flavonoids, have been shown to decrease the risk associated with breast, liver, colorectal, and upper-digestive cancers in epidemiologic studies. Onions are high in flavonoid content and one of the most common vegetables. Additionally, onions are used in most Canadian cuisines.Methods: We investigated the effect of five prominent Ontario grown onion (Stanley, Ruby Ring, LaSalle, Fortress, and Safrane) extracts on two subtypes of breast cancer cell lines: a triple negative breast cancer line MDA-MB-231 and an ER+ breast cancer line MCF-7.Results: These onion extracts elicited strong anti-proliferative, anti-migratory, and cytotoxic activities on both the cancer cell lines. Flavonoids present in these onion extracts induced apoptosis, cell cycle arrest in the G2/M phase, and a reduction in mitochondrial membrane potential at dose-dependent concentrations. Onion extracts were more effective against MDA-MB-231 compared to the MCF-7 cell line. Conclusion: In this study, we investigated the extracts synthesized from Ontario-grown onion varieties in inducing anti-migratory, cytostatic, and cytotoxic activities in two sub-types of human breast cancer cell lines. Anti-tumor activity of these extracts depends upon the varietal and can be formulated into nutraceuticals and functional foods for the wellbeing of cancer patients. Overall, the results suggest that onion extracts are a good source of flavonoids with anti-cancerous properties.Keywords: onion extracts; flavonoids; anti-proliferative; breast cancer; cytotoxic activity

Thieno[2,3-d]pyrimidin-4(3H)-one Derivatives of Benzimidazole as Potential Anti-Breast Cancer (MDA-MB-231, MCF-7) Agents.

2020 ◽  
Vol 20 ◽  
Author(s):  
Stefan Dimov ◽  
Anelia Ts. Mavrova ◽  
Denitsa Yancheva ◽  
Biliana Nikolova ◽  
Iana Tsoneva
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Mechanism Of Action ◽  
Biologically Active ◽  
Breast Cancer Cell Lines ◽  
3T3 Cells ◽  
Fluorescence Study ◽  
Compound 21 ◽  
Mutational Activation ◽  
Mcf 7

Aims: The purpose was the synthesis of some new thienopyrimidines derivative of 1,3-disubstituted benzimidazoles and the evaluation of their cytotoxicity towards MDA-MB-231 and MCF-7 cell lines as well 3T3 cells. Background: An overexpression or mutational activation of TK receptors EGFR and HER2/neu are characteristic for tumors. It has been found that some thieno[2,3-d]pyrimidines exhibit better inhibitory activity against epidermal growth factor receptor (EGFR/ErbB-2) tyrosine kinase in comparison to aminoquinazolines. Breast cancer activity towards MDAMB-231 and MCF-7 cell lines by inhibiting EGFR was revealed by a novel 2-arylbenzimidazole. This motivated the synthesis of new thienopyrimidines possessing benzimidazole fragment in order to evaluate their cytotoxicity to the above mentioned cell lines. Objective: The objectives were the design and synthesis of a novel series thieno[2,3-d]pyrimidines bearing biologically active moieties as 1,3-disubstituted-benzimidazole heterocycle structurally similar to diaryl ureas in order to evaluate their cytotoxicity against MDA-MB-231, MCF-7 breast cancer cell lines. Methods: N,N-disubstituted benzimidazole-2-one carbonitriles were synthesized by Aza-Michael addition and used as precursors to generate some of the new thieno[2,3-d]pyrimidines in acidic medium. The interaction of chloroethyl-2- thienopyrimidines and 2-amino-benzimidazole resp. benzimidazol-2-one nitriles under solid-liquid transfer catalysis conditions lead to obtaining of new thienopyrimidines. MTT assay for cells survival was performed in order to establish the cytotoxicity of the tested compounds. Fluorescence study was used to elucidate some aspect of mechanism. Results: The effect of nine of the synthesized compounds was investigated towards MDA-MB-231 and MCF-7 cells as well as to 3T3 cells. Thieno[2,3-d]pyirimidine-4-one 16 (IC50 – 0.058 μM) and 21 (IC50 – 0.029 μM) possess high cytotoxicity against MDA-MB-231 cells after 24h. The most toxic against breast cancer MCF-7 cells was compounds 21 (IC50 – 0.074 μM), revealing lower cytotoxicity towards mouse fibroblast 3T3 cells with IC50 – 0.20 μM. SAR analisys was performed. Fluorescence study of the treatment of MDA-MB cells with compound 21 was carried out in order to clarify some aspects of mechanism of action. Conclusion: The relationship between cytotoxicity of compounds 14 and 20 against MCF-7 and 3T3 cells can suggest a similar mechanism of action. The antitumor potential of the tested compounds proves the necessity for further investigation to estimate the exact inhibition pathway in the cellular processes. The fluorescence study of the treatment of MDA-MB cells with compound 21 showed a rapid process of apoptosis.

scholarly journals Factors modulating integrin Beta I expression on the breast cancer cell lines MCF-7 and MDA-MB-231

2000 ◽  
Vol 2 (S1) ◽  
Author(s):  
CJ Pogson ◽  
CMW Chan ◽  
L-A Martin ◽  
GPH Gui ◽  
M Dowsett
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Mcf 7
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