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)][CF(3)SO(3)], 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 apoptosis 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.
Valentini
Alessandra
A
Department of Laboratory Medicine, UOC Clinical Molecular Biology, PTV-Hospital University Tor Vergata, Via Oxford 81, 00133 Rome, Italy. ales_valentini@yahoo.it
Conforti
Franco
F
Crispini
Alessandra
A
De Martino
Angelo
A
Condello
Rossella
R
Stellitano
Chiara
C
Rotilio
Giuseppe
G
Ghedini
Mauro
M
Federici
Giorgio
G
Bernardini
Sergio
S
Pucci
Daniela
D
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D004249:DNA Damage; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D016877:Oxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010165:Palladium / Q000737:chemistry / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet
D000970:Antineoplastic Agents; D016877:Oxidants; D017382:Reactive Oxygen Species; D010165:Palladium; D048670:MAP Kinase Kinase 4; D003474:Curcumin