Delayed activation of PKCδ and NFκB and higher radioprotection in splenic lymphocytes by copper (II)–Curcumin (1:1) complex as compared to curcumin

Abstract

A mononuclear 1:1 copper complex of curcumin had been found to be superior to curcumin in its anti-oxidant properties. This paper describes the radio-protective effects of the complex in splenic lymphocytes from swiss mice. The complex was found to be very effective in protecting the cells against radiation-induced suppression of glutathione peroxidase, catalase and superoxide dismutase (SOD) activities. Both curcumin and the complex protected radiation-induced protein carbonylation and lipid peroxidation in lymphocytes with the complex showing better protection than curcumin. It also showed better overall protection by decreasing the radiation-induced apoptosis. The kinetics of activation of PKCdelta and NFkappaB after irradiation in presence or absence of these compounds was looked at to identify the molecular mechanism involved. The modulation of irradiation-induced activation of PKCdelta and NFkappaB by curcumin and the complex was found different at later time periods although the initial response was similar. The early responses could be mere stress responses and the activation of crucial signaling factors at later time periods may be the determinants of the fate of the cell. In this study this delayed effect was observed in case of complex but not in case of curcumin. The delayed effect of the complex along with the fact that it is a better free radical scavenger must be the reason for its better efficacy. The complex was also found to be less cytotoxic then curcumin at similar concentration.

A liquid chromatography–tandem mass spectrometric method for quantification of curcuminoids in cell medium and mouse plasma

“…It can form complexes with metal ions e.g. cupuric [21] ion due to the presence of the ortho methoxy, phenolic and diketo groups in the molecule, which has been proposed to be one of the possible mechanisms for its instability when it is added to the solutions containing metal ions like PBS, cell medium, and plasma. Also, curcumin contains two active double bonds, which are active towards nucleophilic functional groups e.g.…”

Curcumin induces apoptosis through an ornithine decarboxylase-dependent pathway in human promyelocytic leukemia HL-60 cells

“…It seems that both ODC and NF-κB simultaneously exhibit a capacity for chemoresistance. Moreover, curcumin inhibits PKC δ activity and its downstream signaling pathway, transcription factor AP-1 (Balasubramanian and Eckert, 2007;Kunwar et al, 2007). The PKC δ inhibitor, rottlerin, represses ODC activity induced by prolactin in HL-60 cells and stimulates apoptosis of hematopoietic cell lines (Hsu et al, 2006;.…”

Cell Signaling through Protein Kinase C Oxidation and Activation

“…IκBα after degradation is known to release NF-κB, which acts in the nucleus as a transcription factor for many anti-apoptotic genes, thus indicating that the cell could be entering into a cytoprotective pathway. In this study, pretreatment of irradiated cells with curcumin-copper complex was shown to be effective in avoiding radiation-induced damage in these cells [60]. …”