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Insights into the in vitro Anticancer Effects of Diruthenium‐1
Author(s) -
KocevaChyła Aneta,
Matczak Karolina,
Hikisz Msc. Paweł,
Durka Msc. Kamil,
Kochel Msc. Krzysztof,
SüssFink Georg,
Furrer Julien,
Kowalski Konrad
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201600315
Subject(s) - apoptosis , cytotoxicity , chemistry , dna fragmentation , cell cycle , cell cycle checkpoint , fragmentation (computing) , cytotoxic t cell , dna damage , cell culture , microbiology and biotechnology , programmed cell death , cell growth , intracellular , reactive oxygen species , mitosis , in vitro , biology , biochemistry , dna , ecology , genetics
The in vitro anticancer activity of the dinuclear trithiolato‐bridged arene ruthenium complex diruthenium‐1 (DiRu‐1) was evaluated against a panel of human cancer cell lines used as in vitro models for hepatocellular carcinoma (HepG2 cells), estrogen‐responsive breast adenocarcinoma (MCF‐7 cells), and triple‐negative breast adenocarcinoma (MDA‐MB‐231 cells). DiRu‐1 is highly cytotoxic to these cell lines, demonstrating half‐maximal inhibitory concentrations (IC 50 ) in the low‐nanomolar range (77±1.4 to 268.2±4.4 n m ). The main molecular mechanisms responsible for the high cytotoxicity of DiRu‐1 against the most responsive MCF‐7 cell line (IC 50 =77±1.4 n m) were investigated on the basis of the capacity of DiRu‐1 to induce oxidative stress, apoptosis, and DNA damage, and to inhibit the cell cycle and proliferation. The results show that DiRu‐1 triggers caspase‐dependent apoptosis in MCF‐7 cells on both the intrinsic and extrinsic pathways. Moreover, the Ru complex also causes necrosis, mitotic catastrophe, and autophagy. DiRu‐1 increases the intracellular levels of reactive oxygen species (ROS), which play a significant role in its cytotoxicity and pro‐apoptotic activity. An important mechanism of the anticancer activity of DiRu‐1 appears to be the induction of DNA lesions, mainly due to apoptotic DNA fragmentation and cell‐cycle arrest at the G 2 /M checkpoint. These changes are correlated with the concentration of DiRu‐1, the duration of the cell treatment, and the post‐treatment time.