Investigation of the cytotoxicity of newly synthesized complexes of palladium(II) with Schiff bases derived from salicyl-aldehyde on prostate cancer cells in vitro

[D. N. Pantić]

89 listova

Kao prelazni metal paladijum ima mogućnost da gradi kompleksna jedinjenja, stoga, sintetisan je veliki broj kompleksa paladijuma sa različitim ligandima, a sve u cilju ispitivanja antitumorskog efekta kao i selektivnosti potencijalnih hemioterapeutika. Ovakva jedinjenja su pokazala veoma snažan antiproliferativni efekat na različite kancerske ćelije. Stoga cilj naše studije je definisanje antiproliferativnog dejstva tri sintetisana Pd(II) kompleksa koja smo obeležili kao Pd1(C28H24N2O4Pd), Pd2(C30H28N2O4Pd) i Pd3(C34H30N4O2Pd) na ćelije DU-145- i PC-3 (ćelijske linije karcinoma prostate). Metode korišćene u našoj studiji su MTT test, apoptotski test, detekcija ćelijske deobe primenom PI bojenja i analiza regulatornih molekula unutrašnjeg mitohondrijalnog puta. Sistematskom analizom podataka studija je dokazala da sva tri Pd(II) jedinjenja poseduju snažan antiproliferativni efekat na maligne ćelije prostate. Sa druge strane, navedna jedinjenja pokazuju veoma slab antiproliferativni efekat na fibroblaste. Smanjenje vijabilnosti testiranih kancerskih ćelija od strane Pd(II) kompleksa je uslovljeno indukcijom rane apoptoze. Osim toga, testirana jedinjenjea dovode i do zastoja u ćelijskom ciklusu. Apoptoza je aktivirana mitohondrijalnim putem pri čemu se unutar ćelije menja odnos Bax/Bcl-2, što će u daljoj kaskadnoj reakciji usloviti aktivaciju akspaze 3. Testirani kompleski su demonstrirali osim antiproliferativnog i antimetastatski efekat.

As a transition metal, palladium can form complex compounds; therefore, a large number of palladium complexes with different ligands have been synthesized to test the antitumor effect and selectivity of potential chemotherapeutics. Such compounds have shown a powerful antiproliferative effect on various cancer cells. Therefore, our study aims to define the antiproliferative effect of three synthesized Pd(II) complexes, which we have designated as Pd1(C28H24N2O4Pd), Pd2 (C30H28N2O4Pd), and Pd3(C34H30N4O2Pd) on DU-145 and PC-3 cells (prostate carcinoma cell lines). The methods used in our study are MTT assay, apoptosis assay, detection of cell division using PI staining, and analysis of regulatory molecules of the intrinsic mitochondrial pathway. By systematic analysis of the data, the study demonstrated that all three Pd(II) compounds have a strong antiproliferative effect on malignant prostate cells. On the other hand, the compounds show a very weak antiproliferative effect on fibroblasts. The reduction in the viability of the tested cancer cells by the Pd(II) complexes was due to the induction of early apoptosis. In addition, the tested compounds also led to cell cycle arrest. Apoptosis is activated by the mitochondrial pathway, whereby the Bax/Bcl-2 ratio changes within the cell, which, in a further cascade reaction, will cause the activation of caspase 3. The tested complexes demonstrated, in addition to the antiproliferative effect, an antimetastatic effect.

616-006.6:611.63 611.63

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