ABSTRACT
As part of our interest into the bioinorganic chemistry of gallium, gallium(III) complexes of the azole ligands 2,1,3-benzothiadiazole (btd), 1,2,3-benzotriazole (btaH), and 1-methyl-4,5-diphenylimidazole (L) have been isolated. Reaction of btaH or btd with GaBr(3) or GaCl(3) resulted in the mononuclear complexes [GaBr(3)(btaH)(2)] (1) and [GaCl(3)(btd)(2)] (2), respectively, while treatment of GaCl(3) with L resulted in the anionic complex (LH)(2)[GaCl(4)] (3). All three complexes were characterized by single-crystal X-ray crystallography and IR spectroscopy, while their antiproliferative activities were investigated against a series of human and mouse cancer cell lines.
ABSTRACT
Genistein, a natural isoflavone product has been shown to induce cellular death and increase the apoptotic cell death induced by several DNA-damaging stimuli. We have explored the combined effect of genistein and camptothecins against three cell lines, HeLa (cervical cancer), OAW-42 (ovarian cancer) and L929 (normal fibroblasts). Combined effect was estimated in 96-well plates using the SRB method and median-effect analysis. Addition of genistein synergistically increased the antiproliferative affect of camptothecins, inhibiting the camptothecin-induced G2/M arrest and increasing the apoptotic cell population. In HeLa cells, genistein inhibited CDK1 phosphorylation after irinotecan treatment. Thus, abrogation of the G2/M checkpoint control by genistein may be a useful maneuver to increase cytotoxicity of agents that damage DNA and inhibit cell-cycle progression in the G2/M boundary.
