Synergistic action of cisplatin and echistatin in MDA-MB-231 breast cancer cellsReportar como inadecuado




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Molecular and Cellular Biochemistry

, Volume 427, Issue 1–2, pp 13–22

First Online: 19 December 2016Received: 23 June 2016Accepted: 02 December 2016DOI: 10.1007-s11010-016-2894-8

Cite this article as: Czarnomysy, R., Surażyński, A., Popławska, B. et al. Mol Cell Biochem 2017 427: 13. doi:10.1007-s11010-016-2894-8

Abstract

The aim of our study was to determine whether the use of cisplatin in the presence echistatin in MDA-MB-231 breast cancer cells leads to a reduction of toxic effects associated with the use of cisplatin. The expression of β1-integrin and insulin-like growth factor 1 receptor IGF-IR, signaling pathway protein expression: protein kinase B AKT, mitogen-activated protein kinases ERK1-ERK2, nuclear factor kappa B NFκB, and caspase-3 and -9 activity was measured after 24 h of incubation with tested compounds to explain detailed molecular mechanism of induction of apoptosis. The viability of MDA-MB-231 breast cancer cells was determined by 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Annexin V-FITC-propidium iodide staining assay was performed to detect the induction of apoptosis. Inhibition DNA biosynthesis was determined by Hthymidine incorporation into DNA. The expression of of β1-integrin, IGF-IR, AKT, ERK1-ERK2, NFκB, caspase-3 and -9 was evaluated using Western blot. The results suggest that treatment of MDA-MB-231 breast cancer cells for 24 h cisplatin plus echistatin severely inhibits cell growth and activates apoptosis by upregulation of caspase-3 and -9 expressions. The effect was stronger than treatment cisplatin and echistatin alone. In this study, we have found that cisplatin plus echistatin treatment decreases collagen biosynthesis in MDA-MB-231 breast cancer cells stronger than the individual compounds. The inhibition was found to be dependent on the β1-integrin and IGF receptor activation. A significant reduction of ERK1-ERK2, AKT expression in cancer cells after cisplatin plus echistatin treatment was also found. The cancer cells treated by echistatin, cisplatin, and in particular the combination of both compounds drastically increased expression of NFκB transcription factor. Our results suggest that combined therapy cisplatin plus echistatin is a possible way to improve selectiveness of cisplatin. This mechanism probably is due to downregulation of expression of β1-integrin and IGF-IR receptors, and the signaling pathway proteins induced by these receptors. Our results suggest that therapy cisplatin plus echistatin is a possible way to improve selectiveness of cisplatin.

KeywordsBreast cancer cells Cisplatin Echistatin Apoptosis Cell signaling  Download fulltext PDF



Autor: Robert Czarnomysy - Arkadiusz Surażyński - Bożena Popławska - Edyta Rysiak - Natalia Pawłowska - Anna Czajkowska - Krzy

Fuente: https://link.springer.com/



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