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In-vitro and in-vivo evaluation of the anticancer activity of diruthenium-2, a new trithiolato arene ruthenium complex [(eta(6)-p-MeC6H4Pri)(2)Ru-2(mu-S-p-C6H4OH)(3)]Cl
Autoři: Muthna Darina | Tomsik Pavel | Havelek Radim | Kohlerova Renata | Kasilingam Vidhya | Cermakova Eva | Stibal David | Rezacova Martina | Suss-Fink Georg
Rok: 2016
Druh publikace: článek v odborném periodiku
Název zdroje: Anti-Cancer Drugs
Strana od-do: 643-650
Tituly:
Jazyk Název Abstrakt Klíčová slova
cze In-vitro a in-vivo hodnocení protinádorové aktivity diruthenia 2, nového trithiolato arene rutheniového complexu [(eta(6)-p-MeC6H4Pri)(2)Ru-2(mu-S-p-C6H4OH)(3)]Cl Práce se zabývá in-vitro a in-vivo hodnocením protinádorové aktivity nového trithiolato arene rutheniového complexu [(eta(6)-p-MeC6H4Pri)(2)Ru-2(mu-S-p-C6H4OH)(3)]Cl, zvaného diruthenium 2. Protinádorová aktivita; nádor prsu; dvojvláknové zlomy DNA; Ehrlichův tumor; In-vitro a in-vivo studie; Rutheniové komlexy
eng In-vitro and in-vivo evaluation of the anticancer activity of diruthenium-2, a new trithiolato arene ruthenium complex [(eta(6)-p-MeC6H4Pri)(2)Ru-2(mu-S-p-C6H4OH)(3)]Cl In the present study, we investigated the anticancer action of the trithiolato arene ruthenium complex, [(η6-p-MeC6H4Pri)2Ru2(μ-S-p-C6H4OH)3]Cl, named diruthenium-2, both in vitro and in vivo. The mechanism of antiproliferative, cytotoxic, and DNA-damaging activity, and the effect on expressions of cell cycle regulatory proteins were investigated using a WST-1-based proliferation assay, lactate dehydrogenase leakage assay, comet assay, flow cytometry, and western blot analysis. In-vivo anticancer activity was evaluated using Ehrlich tumor-bearing NMRI mice. Diruthenium-2 inhibited the growth of all cancer cell lines used, the most sensitive being gastric (AGS), breast cancer (BT-549, MCF-7, MDA-MB-231), and leukemic (HL- 60, MOLT-4) cells. In MCF-7 cells, it caused a G1/S cell cycle arrest, along with an increase in the expression of protein p21 and cyclin B1. We also observed increased levels of MRN complex proteins, which, together with the results from the comet assay, indicate the formation of DNA double-strand breaks. In tumor-bearing mice, diruthenium-2 at doses of 3 and 5 mg/kg inhibits the growth of solid Ehrlich tumor, although weaker than cisplatin. However, it did not prolong the post-therapeutic survival. Our results suggest the in-vitro potential of diruthenium-2 should be further evaluated in studies using other in-vivo models. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Anticancer activity; Breast cancer; DNA double-strand breaks; Ehrlich tumor; In vitro and in vivo study; Ruthenium complexes