Bioquímica e Farmacologia: Acesso Aberto
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Abstrato

The Influence of Anti-MUC1 with Berenil Complex of Platinum(II) on Concentration of Apoptotic Markers in Human Skin Fibroblasts

Gornowicz A, Bielawska A, Gabryel-Porowska H and Bielawski K

MUC1 mucin is a type I transmembrane glycoprotein expressed at the apical border of healthy epithelia that line the respiratory, reproductive and gastrointestinal tracts and is overexpressed in various cancer cells. The goal of the study was to check the effect of berenil complex of Platinum(II) applied together with anti-MUC1 antibody on induction of programmed cell death in human skin fibroblasts. The influence of novel platinum(II) complex used with anti-MUC1 on the concentration of selected markers of apoptosis such as p53, Bax, cytochrome c, caspase-8, -9 and caspase-3 was determined using the ELISA technique. The results from combined treatment were compared with those obtained using monotherapy and combined treatment with cisplatin and anti-MUC1. In our study we observed that combined treatment of Pt12 with anti-MUC1 had no influence on the induction of programmed cell death in normal cells such as human skin fibroblasts. Also, we showed that cisplatin in dose 20 μM strongly induced apoptosis in human skin fibroblasts. We observed higher concentrations of all tested apoptotic markers such as Bax protein, p53, caspases-3,-8,-9. The proapoptotic effect was weaker after the combined treatment of cisplatin together with anti-MUC1. The obtained results proved that only cisplatin in dose 20 μM induced both apoptotic pathways. It activated the death receptor pathway associated with higher concentration of caspase-8 as well as mitochondrial pathway connected with cytochrome c and caspase-9 releasement. On the contrary cisplatin used together with anti-MUC1 induced only death receptor pathway. We observed higher concentration of caspase-8 in cell lysates as compared with that in control group. The novel Platinum(II) complex together with anti-MUC1 showed no harming effect in the normal cells. Taken together, our results suggest that the combined treatment with anti- MUC1 is a possible way to improve selectiveness of chemotherapeutic agent.