curcumin and Histiocytoma--Benign-Fibrous

We have synthesized different bioconjugates of curcumin, which were tested for their pro- and antioxidant properties. In the present study five representative derivatives of curcumin, i.e., 4,4'-di-(O-acetyl) curcumin, 4,4'-di-(O-glycinoyl) curcumin, 4,4'-di-(O-glycinoyl-di-N-piperoyl) curcumin, 4,4'-di-(O-piperoyl) curcumin, and 4,4'-(O,O-cystinoyl)-3,3'-dimethoxydiphenyl-1,6-heptadiene-3,5-dione, were used for testing their apoptotic potential on tumor cells. Dipiperoyl and diglycinoyl derivatives showed higher apoptotic activity at lower concentrations, whereas diacetyl curcumin had slightly lower apoptotic activity on tumor cells. On the other hand, diglycinoyl-dipiperoyl and cystinoyl heptadiene derivatives had lost their apoptotic potential significantly. The apoptotic activity of these derivatives correlated very well with the generation of ROS by the tumor cells, whereas GSH levels remained unaltered. Our studies also indicate downregulation of Bcl-2 and participation of caspase-3 in the apoptotic death of tumor cells.

Topics: Animals; Antineoplastic Agents; Apoptosis; Caspase 3; Caspases; Curcumin; Down-Regulation; Glutathione; Histiocytoma, Benign Fibrous; Oxidation-Reduction; Proto-Oncogene Proteins c-bcl-2; Rats; Reactive Oxygen Species; Tumor Cells, Cultured

Curcumin, the active ingredient of the rhizome of Curcuma longa has anti-inflammatory, antioxidant and antiproliferative activities. Although its precise mode of action remains elusive, studies have shown that chemopreventive action of curcumin might be due to its ability to induce apoptosis in cancer cells. Curcumin was shown to be responsible for the inhibition of AK-5 tumor (a rat histiocytoma) growth by inducing apoptosis in AK-5 tumor cells via caspase activation. This study was designed to investigate the mechanism leading to the induction of apoptosis in AK-5 tumor cells. Curcumin treatment resulted in the hyperproduction of reactive oxygen species (ROS), loss of mitochondrial membrane potential (delta psi(m)) and cytochrome c release to the cytosol, with the concomitant exposure of phosphatidylserine (PS) residues on the cell surface. This study suggests redox signalling and caspase activation as the mechanisms responsible for the induction of curcumin mediated apoptosis in AK-5 tumor cells.

Topics: Animals; Antineoplastic Agents; Apoptosis; Caspases; Cell Membrane; Curcumin; Cytochrome c Group; DNA Fragmentation; Enzyme Activation; Histiocytoma, Benign Fibrous; Intracellular Membranes; Membrane Potentials; Mitochondria; Oxidation-Reduction; Phosphatidylserines; Rats; Rats, Wistar; Reactive Oxygen Species; Signal Transduction; Superoxides; Tumor Cells, Cultured

Rats were fed turmeric at various levels in the diet for up to 3 months and then exposed to benzo[a]pyrene (B[a]P) or 3-methylcholanthrene (3-MC) by ip injection. Urinary mutagens were detected using the Salmonella typhimurium assay. Turmeric fed at 0.5% and above inhibited B[a]P- and 3-MC-mediated mutagenicity. Turmeric did not adversely affect the food intake, or weight gain of the rats and no histological changes were detected. These findings are significant in view of the widespread exposure of humans to polycyclic aromatic hydrocarbons. The study has also revealed a useful in vivo model for testing the antimutagenicity.

Topics: Administration, Oral; Animals; Benzo(a)pyrene; Body Weight; Curcumin; Dose-Response Relationship, Drug; Histiocytoma, Benign Fibrous; Male; Methylcholanthrene; Mutagenicity Tests; Mutagens; Rats; Rats, Inbred Strains