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Anti-cancer activity of di- and tri-organotin(IV) compounds with D-(+)-Galacturonic acid on human tumor cells.

Authors :
Attanzio A
Ippolito M
Girasolo MA
Saiano F
Rotondo A
Rubino S
Mondello L
Capobianco ML
Sabatino P
Tesoriere L
Casella G
Source :
Journal of inorganic biochemistry [J Inorg Biochem] 2018 Nov; Vol. 188, pp. 102-112. Date of Electronic Publication: 2018 Apr 09.
Publication Year :
2018

Abstract

We have compared the anti-proliferative activity in vitro, of R <subscript>2</subscript> SnGala (1-3) [R = Me, n-Bu, Ph] and novel R <subscript>3</subscript> SnGala (4, 5) [R = Me, n-Bu] with D-(+)-Galacturonic acid [HGala; Gala <superscript>q-</superscript> , q = (2) and (1) for R <subscript>2</subscript> SnGala and R <subscript>3</subscript> SnGala, respectively] compounds, towards human tumor cell lines of intestinal carcinoma (HCT-116) and breast adenocarcinoma (MCF-7). The new synthesized 4 and 5 compounds were characterized, in solution, by <superscript>1</superscript> H, <superscript>13</superscript> C and <superscript>119</superscript> Sn NMR, that showed that HGala acts as monoanionic moiety and evidenced the dynamic behavior of the compounds, due to inter-conversions involving the anomeric carbon atom of the ligand. Cell viability, apoptosis induction and cell cycle distribution were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay and flow cytometry, respectively. The cytotoxicity of the compounds, in the micro-submicromolar range, changed in the order of the organotin(IV) moieties, according to 5 > 3 > 2, while 1 and 4, containing Me <subscript>n</subscript> Sn(IV) (n = 2,3) moieties, were ineffective. Compound 5 showed peculiar cytotoxic effects. It did not cause time dependent inhibition of cell growth nor accumulated into the cells. Cell death induced by the active 2, 3, and 5, was shown to be apoptotic by measuring the exposure of phosphatidylserine to the outer membrane and the loss of mitochondrial potential. All the cytotoxic compounds induced an accumulation of cells in the subG0/G1phase, while only 2 and 3 perturbed the cell cycle confining viable cells in G0/G1phase. Finally, none of the compounds investigated affected the viability of normal intestinal or liver cells, indicating selectivity towards tumor cells.<br /> (Copyright © 2018. Published by Elsevier Inc.)

Details

Language :
English
ISSN :
1873-3344
Volume :
188
Database :
MEDLINE
Journal :
Journal of inorganic biochemistry
Publication Type :
Academic Journal
Accession number :
29807841
Full Text :
https://doi.org/10.1016/j.jinorgbio.2018.04.006