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Benzene-poly-carboxylic acid complex, a novel anti-cancer agent induces apoptosis in human breast cancer cells.

Fares F, Azzam N, Fares B, Larsen S, Lindkaer-Jensen S - PLoS ONE (2014)

Bottom Line: Caspases were detected by western blot analysis and gene expression was measured by using the Applied Biosystems® TaqMan® Array Plates.The results showed that exposure of the cells to BP-C1 for 48 h, significantly (P<0.001) reduced cell viability, induced apoptosis and activated caspase 8 and caspace 9.Moreover, gene expression experiments indicated that BP-C1 increased the expression of pro-apoptotic genes (CASP8AP1, TNFRSF21, NFkB2, FADD, BCL10 and CASP8) and lowered the level of mRNA transcripts of inhibitory apoptotic genes (BCL2L11, BCL2L2 and XIAP.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Biology, Faculty of Natural Sciences, University of Haifa, and Department of Molecular Genetics, Carmel Medical Center, Haifa, Israel.

ABSTRACT
Some cases of breast cancer are composed of clones of hormonal-independent growing cells, which do not respond to therapy. In the present study, the effect of Benzene-Poly-Carboxylic Acid Complex (BP-C1) on growth of human breast-cancer cells was tested. BP-C1 is a novel anti-cancer complex of benzene-poly-carboxylic acids with a very low concentration of cis-diammineplatinum (II) dichloride. Human breast cancer cells, MCF-7 and T47D, were used. Cell viability was detected by XTT assay and apoptosis was detected by Flow Cytometry and by annexin V/FITC/PI assay. Caspases were detected by western blot analysis and gene expression was measured by using the Applied Biosystems® TaqMan® Array Plates. The results showed that exposure of the cells to BP-C1 for 48 h, significantly (P<0.001) reduced cell viability, induced apoptosis and activated caspase 8 and caspace 9. Moreover, gene expression experiments indicated that BP-C1 increased the expression of pro-apoptotic genes (CASP8AP1, TNFRSF21, NFkB2, FADD, BCL10 and CASP8) and lowered the level of mRNA transcripts of inhibitory apoptotic genes (BCL2L11, BCL2L2 and XIAP. These findings may lead to the development of new therapeutic strategies for treatment of human cancer using BP-C1 analog.

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Related in: MedlinePlus

Effects of BP-C1 on annexin V level on MCF-7 CELLS.Cells were treated with BP-C1 (750 µg/ml) for 48 h and Flow cytometric analysis of annexin V-FITC/PI double-stained was performed. In each plot, the lower left quadrant (Q3) represents viable cells, the upper left quadrant (Q1) indicates necrotic cells, the lower right quadrant (Q4) denotes early apoptotic cells, and the upper right quadrant (Q2) represents necrotic or late apoptotic cells.
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pone-0085156-g003: Effects of BP-C1 on annexin V level on MCF-7 CELLS.Cells were treated with BP-C1 (750 µg/ml) for 48 h and Flow cytometric analysis of annexin V-FITC/PI double-stained was performed. In each plot, the lower left quadrant (Q3) represents viable cells, the upper left quadrant (Q1) indicates necrotic cells, the lower right quadrant (Q4) denotes early apoptotic cells, and the upper right quadrant (Q2) represents necrotic or late apoptotic cells.

Mentions: Annexin V-FITC binding analysis and PI staining were performed to quantify cell death arising from apoptosis and necrosis, respectively. The number of intact cells was significantly decreased in the treated cells with BP-C1 compared to the control cells as shown in Fig. 3 and Fig. 4. Treatment with BP-C1 significantly increased (P<0.05) the number of Annexin V-FITC-positive/PI-positive cells. Respective percentages of these cells (Q2+Q4) after treatment with 750 µg/ml for 48 h were: 69% vs. 9%, for MCF-7 cells (Fig. 3) and 81% vs. 15% of T47D cells (Fig. 4).


Benzene-poly-carboxylic acid complex, a novel anti-cancer agent induces apoptosis in human breast cancer cells.

Fares F, Azzam N, Fares B, Larsen S, Lindkaer-Jensen S - PLoS ONE (2014)

Effects of BP-C1 on annexin V level on MCF-7 CELLS.Cells were treated with BP-C1 (750 µg/ml) for 48 h and Flow cytometric analysis of annexin V-FITC/PI double-stained was performed. In each plot, the lower left quadrant (Q3) represents viable cells, the upper left quadrant (Q1) indicates necrotic cells, the lower right quadrant (Q4) denotes early apoptotic cells, and the upper right quadrant (Q2) represents necrotic or late apoptotic cells.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921106&req=5

pone-0085156-g003: Effects of BP-C1 on annexin V level on MCF-7 CELLS.Cells were treated with BP-C1 (750 µg/ml) for 48 h and Flow cytometric analysis of annexin V-FITC/PI double-stained was performed. In each plot, the lower left quadrant (Q3) represents viable cells, the upper left quadrant (Q1) indicates necrotic cells, the lower right quadrant (Q4) denotes early apoptotic cells, and the upper right quadrant (Q2) represents necrotic or late apoptotic cells.
Mentions: Annexin V-FITC binding analysis and PI staining were performed to quantify cell death arising from apoptosis and necrosis, respectively. The number of intact cells was significantly decreased in the treated cells with BP-C1 compared to the control cells as shown in Fig. 3 and Fig. 4. Treatment with BP-C1 significantly increased (P<0.05) the number of Annexin V-FITC-positive/PI-positive cells. Respective percentages of these cells (Q2+Q4) after treatment with 750 µg/ml for 48 h were: 69% vs. 9%, for MCF-7 cells (Fig. 3) and 81% vs. 15% of T47D cells (Fig. 4).

Bottom Line: Caspases were detected by western blot analysis and gene expression was measured by using the Applied Biosystems® TaqMan® Array Plates.The results showed that exposure of the cells to BP-C1 for 48 h, significantly (P<0.001) reduced cell viability, induced apoptosis and activated caspase 8 and caspace 9.Moreover, gene expression experiments indicated that BP-C1 increased the expression of pro-apoptotic genes (CASP8AP1, TNFRSF21, NFkB2, FADD, BCL10 and CASP8) and lowered the level of mRNA transcripts of inhibitory apoptotic genes (BCL2L11, BCL2L2 and XIAP.

View Article: PubMed Central - PubMed

Affiliation: Department of Human Biology, Faculty of Natural Sciences, University of Haifa, and Department of Molecular Genetics, Carmel Medical Center, Haifa, Israel.

ABSTRACT
Some cases of breast cancer are composed of clones of hormonal-independent growing cells, which do not respond to therapy. In the present study, the effect of Benzene-Poly-Carboxylic Acid Complex (BP-C1) on growth of human breast-cancer cells was tested. BP-C1 is a novel anti-cancer complex of benzene-poly-carboxylic acids with a very low concentration of cis-diammineplatinum (II) dichloride. Human breast cancer cells, MCF-7 and T47D, were used. Cell viability was detected by XTT assay and apoptosis was detected by Flow Cytometry and by annexin V/FITC/PI assay. Caspases were detected by western blot analysis and gene expression was measured by using the Applied Biosystems® TaqMan® Array Plates. The results showed that exposure of the cells to BP-C1 for 48 h, significantly (P<0.001) reduced cell viability, induced apoptosis and activated caspase 8 and caspace 9. Moreover, gene expression experiments indicated that BP-C1 increased the expression of pro-apoptotic genes (CASP8AP1, TNFRSF21, NFkB2, FADD, BCL10 and CASP8) and lowered the level of mRNA transcripts of inhibitory apoptotic genes (BCL2L11, BCL2L2 and XIAP. These findings may lead to the development of new therapeutic strategies for treatment of human cancer using BP-C1 analog.

Show MeSH
Related in: MedlinePlus