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.

Unravelling mechanisms behind the biological activity of bis(S-citronellalthiosemicarbazonato)nickel(ii) / Annamaria Buschini;Silvana Pinelli;Rossella Alinovi;Francesca Mussi;Franco Bisceglie;Claudio Rivetti;Nicola Doniselli;Giorgio Pelosi. - In: METALLOMICS. - ISSN 1756-5901. - 6:(2014), pp. 783-792. [10.1039/c3mt00345k]

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

BUSCHINI, Annamaria;PINELLI, Silvana;ALINOVI, Rossella;MUSSI, FRANCESCA;BISCEGLIE, Franco;RIVETTI, Claudio;DONISELLI, Nicola;PELOSI, Giorgio
2014

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.
Unravelling mechanisms behind the biological activity of bis(S-citronellalthiosemicarbazonato)nickel(ii) / Annamaria Buschini;Silvana Pinelli;Rossella Alinovi;Francesca Mussi;Franco Bisceglie;Claudio Rivetti;Nicola Doniselli;Giorgio Pelosi. - In: METALLOMICS. - ISSN 1756-5901. - 6:(2014), pp. 783-792. [10.1039/c3mt00345k]
File in questo prodotto:
File Dimensione Formato  
Buschini2014.pdf

non disponibili

Tipologia: Documento in Post-print
Licenza: Creative commons
Dimensione 1.51 MB
Formato Adobe PDF
1.51 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11381/2695882
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 6
social impact