Synergistic action of cisplatin and echistatin in MDA-MB-231 breast cancer cells

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 [3H]thymidine 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.

Cell migration inhibition activity of a non-RGD disintegrin from Crotalus durissus collilineatus venom

“…For example, echistatin combined with cisplatin (CDDP) was capable of increasing the expression of nuclear factor kappa B (NFκB), caspase-9 and caspase-3, leading to increased apoptosis in MDA-MB-231 cells. These data suggest that the combination of this disintegrin with CDDP may serve as a new type of anticancer therapy [ 63 ].…”

A novel series of pyrazole-platinum(II) complexes as potential anti-cancer agents that induce cell cycle arrest and apoptosis in breast cancer cells

“…Annexin V bound with high affinity to phosphatidylserine and thus could be used to identify cells in all stages of the programmed cell death. Propidium iodide (PI) stained cells with a disrupted cell membrane, and it could be used to identify late apoptotic and dead cells 13 . Cells cultured in a drug-free medium were used as controls.…”

“…In the case of breast cancer chemotherapy, the method to improve cisplatin selectivity may be combined treatment with cisplatin plus echistatin 13 . Likewise, monoclonal antibody against MUC1 increased the sensitivity of breast cancer cells to the dinuclear platinum(II) complex.…”

Cisplatin-induced autophagy protects breast cancer cells from apoptosis by regulating yes-associated protein

“…Endoplasmic reticulum (ER) stress is involved in cisplatin-induced apoptosis in human lung cancer cells (5). However, cisplatin exhibits limited therapeutic efficacy (6). Therefore, more effective therapeutic options are required.…”