Synthesis, Oxidant Properties, and Antitumoral Effects of a Heteroleptic Palladium(II) Complex of Curcumin on Human Prostate Cancer Cells

A new ionic Pd(II) complex, [(bipy)Pd(Pcurc)][CF3SO3], 1, with the metal center coordinated to two different chelating ligands, the pure curcumin (Pcurc) and the 4,4′-dinonyl-2,2′-bipyridine (bipy), has been synthesized, fully characterized, and its antitumoral mechanism and oxidant property have be...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 2009-01, Vol.52 (2), p.484-491
Main Authors: Valentini, Alessandra, Conforti, Franco, Crispini, Alessandra, De Martino, Angelo, Condello, Rossella, Stellitano, Chiara, Rotilio, Giuseppe, Ghedini, Mauro, Federici, Giorgio, Bernardini, Sergio, Pucci, Daniela
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Biological and medical sciences
Cell Line, Tumor
Cell Proliferation - drug effects
Chromatography, High Pressure Liquid
Curcumin - chemistry
Curcumin - pharmacology
DNA Damage
General aspects
Humans
Male
MAP Kinase Kinase 4 - metabolism
Medical sciences
Oxidants - chemical synthesis
Oxidants - chemistry
Oxidants - pharmacology
Palladium - chemistry
Palladium - pharmacology
Pharmacology. Drug treatments
Prostatic Neoplasms - pathology
Reactive Oxygen Species - metabolism
Signal Transduction - drug effects
Spectrophotometry, Ultraviolet
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A new ionic Pd(II) complex, [(bipy)Pd(Pcurc)][CF3SO3], 1, with the metal center coordinated to two different chelating ligands, the pure curcumin (Pcurc) and the 4,4′-dinonyl-2,2′-bipyridine (bipy), has been synthesized, fully characterized, and its antitumoral mechanism and oxidant property have been investigated. The Pd(II) complex induces both cell growth inhibition and apoptosis of human prostate cancer cells, (LnCaP, PC3, and DU145) through the production of ROS and JNK phosphorylation associated with GSTp1 down-regulation. ROS production induced by complex 1 treatment activated apoptotis through mitochondrial membrane depolarization in all prostate cancer cells, with up-regulation of Bax and down-regulation of Bcl-2 proteins. In addition, while curcumin determines DNA damage and PARP cleavage, complex 1 does not elicit any activation of PARP enzyme. Taken together, these data validate the significance of curcumin complexation to a metal center and its conjugation to another functionalized bioactive ligand in the apoptosis signal transduction and enhancement of cell death in prostate cancer cell lines and suggest the potential of this design strategy in the improvement of the metal-based drugs cytotoxicity.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm801276a