DNA damage and induction of apoptosis in pancreatic cancer cells by a new dinuclear bis(triazacyclonane) copper complex.
J Inorg Biochem
; 145: 101-7, 2015 Apr.
Article
in En
| MEDLINE
| ID: mdl-25660211
ABSTRACT
The dinuclear copper(II) complex [Cu2{bcmp(-H)}(µ-OH)](NO3)2·H2O (1, bcmp=2,6-bis(1,4,7-triazacyclonon-1-ylmethyl)-4-methylphenol) has been synthesized and characterized by electrospray ionization mass spectrometry, potentiometric titration and cyclovoltammetry. The X-ray structure of the analogous perchlorate salt [Cu2{bcmp(-H)}(µ-OH)](ClO4)2·2.5H2O (2) was determined. Cytotoxicity studies showed very promising activity of 1 against various pancreatic tumor cell lines with IC50 values comparable or even lower than those of cisplatin. The Cu complex displayed low toxicity against a human non-tumor cell line (HEK 293) demonstrating selectivity for cancer cells. 1 converts supercoiled pUC19 plasmid DNA into the nicked form at micromolar concentrations in the absence of added reductants. A detailed kinetic study on the hydrolysis of the DNA model bis(2,4-dinitrophenyl) phosphate (BDNPP) has been performed. 1 hydrolyses BDNPP with a second order rate constant of 0.047 M s(-1) at pH 8 and 40 °C. Finally, single cell electrophoresis (comet assay) and fluorescence microscopy analysis showed that 1 interacts with cellular DNA and induces apoptotic cell death of Capan-1 pancreatic cancer cells. Western blotting analysis indicated that the Cu complex activates the p53 dependent pathway of apoptosis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
/
DNA Damage
/
Apoptosis
/
Coordination Complexes
Limits:
Humans
Language:
En
Journal:
J Inorg Biochem
Year:
2015
Document type:
Article
Affiliation country: