Feb 19, 2014

Unravelling mechanisms behind the biological activity of bis(S-citronellalthiosemicarbazonato)nickel(II)

Metallomics : Integrated Biometal Science
Annamaria BuschiniGiorgio Pelosi

Abstract

Bis(S-citronellalthiosemicarbazonato)nickel(II), [Ni(tcitr)2], is a compound that inhibits proliferation of tumour line U937 by inducing a G2/M block and leading the cancer cells to apoptosis. This nickel derivative shows no activity on non proliferating healthy cells. In this paper we report our studies on the action mechanisms of [Ni(tcitr)2]. Apoptosis in U937 cells exposed to [Ni(tcitr)2] takes place through activation of caspase-9, and therefore through an intrinsic triggering mechanism. Given the DNA damage observed in the Comet assay, the mutagenic activity of the metal complex was tested, including with the Ames test, micronuclei and DNA damage recovery, but neither mutagenicity nor recovery were detected. Nickel-complex-DNA interactions were analyzed by direct action of the compound on plasmidic and linear DNA by UV-vis and CD spectroscopy, gel electrophoresis and Atomic Force Microscopy. These experiments reveal that [Ni(tcitr)2] does not cause DNA breaks and does not intercalate, but significantly alters the DNA conformation creating knot-like structures and hairpins.

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Mentioned in this Paper

Caspase-9
Antineoplastic Agents
RNA Conformation
Apoptosis, Intrinsic Pathway
Neoplasms
Tumor Lysis Syndrome
Microscopy, Atomic Force
Procaspase-9
Tumor Cells, Malignant
DNA Breaks

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