In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e12029-e12029
Abstract:
e12029 Background: Breast cancer is the most frequent malignancy in women in western countries and despite progress in the treatment options surgery, radiation, chemotherapy and hormonal therapy it is still the leading cause of cancer death. BP-C1 is a novel anti-cancer complex of benzol-polycarbonic acids with ammonium-platinum salt developed by Meabco ltd, Denmark. Methods: In the present study, the effect of BP-C1 on growth of human breast cancer cells, MCF7 and T47D, was studied. Cells were exposed to different doses of BP-C1, 100-1000 µg/ml, and cell viability, toxicity (LDH release), cell cycle, apoptosis, caspase activation and gene expression were examined. Results: No toxicity was observed. Exposure of the cells to BP-C1 for 48h, significantly (P 〈 0.001) reduced cell viability by approxematly 90% with IC50 of 400 µg/ml. In cell cycle studies cells were accumulated in sub-G1 phase, which may indicate induction of apoptosis. Annexin 5 assay demonstrated that BP-C1 induces apoptosis of MCF-7 and T47D cell by 65% and 34%, respectively, after 48h of treatment. Detection of caspases by western blot analysis revealed that BP-C1 activates caspase 8 and caspase 9. Moreover, gene expression experiments following BP-C1 treatment and using the Applied Biosystems TaqMan Array Plates indicated that BP-C1 caused an increase in the the expression of pro-apoptotic genes; CASP8AP2, TNFRSF21, RELB, NFKB2, BIRC8 and FADD when compared to the expression level of the House keeping genes, HPRT1 and GAPDH. On the other hand, lower levels of mRNA transcripts of the inhibitory apoptotic genes; BCL2L2 and XIAP were detected. Conclusions: These results may indicate that BP-C1 reduced cell viability of human cancer cells by a unigue induction of apoptosis through activation of the extrinsic (death receptors) and the intrinsic (mitochondrion) apoptotic pathways. These findings may lead to the development of new therapeutic strategies for treatment of cancer using BP-C1 or analogs.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.15_suppl.e12029
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
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