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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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Chemical structure of BP-C1 analog.R1 and R2 represent any kind of chain.
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pone-0085156-g001: Chemical structure of BP-C1 analog.R1 and R2 represent any kind of chain.

Mentions: In this study human breast cancer cell lines MCF-7 (wild-type p53) and T47D (p53 mutant) were used to examine the effects of BP-C1 (Fig. 1) on cell proliferation. Cells were treated with BP-C1 (100–1,000 µg/ml) for 48 hours and cell viability was detected by XTT assay. The results indicated that BP-C1 significantly (P<0.001) reduced cell viabilty of MCF7 and T47D cells with IC50 of 370 µg/ml and 490 µg/ml, respectively (Figure 2). In order to exclude the possibility of cytotoxic effects of BP-C1 on the cells, LDH assay was performed as described under “Materials and Methods”. LDH assay is one of the most widely-used and accepted methods for measuring cellular lysis. It was observed that BP-C1, at a concentration of up to 1,500 µg/ml, does not cause a statistically significant change in the LDH level in the media compared with controls (Data not shown). Therefore, for further studies, 750 µg/ml, was used.


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)

Chemical structure of BP-C1 analog.R1 and R2 represent any kind of chain.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0085156-g001: Chemical structure of BP-C1 analog.R1 and R2 represent any kind of chain.
Mentions: In this study human breast cancer cell lines MCF-7 (wild-type p53) and T47D (p53 mutant) were used to examine the effects of BP-C1 (Fig. 1) on cell proliferation. Cells were treated with BP-C1 (100–1,000 µg/ml) for 48 hours and cell viability was detected by XTT assay. The results indicated that BP-C1 significantly (P<0.001) reduced cell viabilty of MCF7 and T47D cells with IC50 of 370 µg/ml and 490 µg/ml, respectively (Figure 2). In order to exclude the possibility of cytotoxic effects of BP-C1 on the cells, LDH assay was performed as described under “Materials and Methods”. LDH assay is one of the most widely-used and accepted methods for measuring cellular lysis. It was observed that BP-C1, at a concentration of up to 1,500 µg/ml, does not cause a statistically significant change in the LDH level in the media compared with controls (Data not shown). Therefore, for further studies, 750 µg/ml, was used.

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