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Several chalcones were synthesized and their in vitro cytotoxicity against various human cell lines, including human breast adenocarcinoma cell line MCF-7, human lung adenocarcinoma cell line A549, human prostate cancer cell line PC3, human adenocarcinoma cell line HT-29 (colorectal cancer) and human normal liver cell line WRL-68 was evaluated. Most of the compounds being active cytotoxic agents, four of them with minimal IC50 values were chosen and studied in detail with MCF-7 cells. The compounds 1, 5, 23, and 25 were capable in eliciting apoptosis in MCF-7 cells as shown by multiparameter cytotoxicity assay and caspase-3/7, -8, and -9 activities (p < 0.05). The ROS level showed 1.3-fold increase (p < 0.05) at the low concentrations used and thus it was concluded that the compounds increased the ROS level eventually leading to apoptosis in MCF-7 cells through intrinsic as well as extrinsic pathways.

In this study the short term (3 months) toxicological effects of varying levels of Catha edulis leaves were examined on the plasma concentration of liver enzymes and the histopathology of tissue sections of various organs including the liver, kidneys, spleen and testis. Both the biochemical and histopathological data demonstrated, initial signs of Catha edulis toxicity. Our results show a significant increase in plasma levels of alkaline phosphatase (ALP) and alanine aminotransferase (ALT) with all levels of Catha edulis leaves tested and throughout the treatment period. The increase of ALP was more prominent than that of ALT. The plasma levels of aspartate aminotransferase (AST) were only moderately increased at the higher dose (30%) in the later stages of treatment. In addition, a time-dependent gradual increase in indirect bilirubin with a concomitant decrease in direct bilirubin levels was observed with the 30% Catha edulis with no signs of haemolysis. The histopathology of tissue sections of the liver displayed evidence of congestion of the central liver veins as well as acute hepatocellular degenerative and regenerative activities in the tissue sections obtained from animals treated with both 20% and 30% Catha edulis. Similarly, histopathological examination of the tissue sections of the kidneys showed some lesions, and the degree of the lesion increased as the dose of Catha edulis leaves increased including: the presence of fat droplets particularly seen in the upper cortical tubules; acute cellular swelling; hyaline tubules; and acute tubular nephrosis. In contrast, Catha edulis treatment did not affect the spleen and increased the rate of spermatogenesis in male rabbits with the spermatozoa being quite evident, the Leydig cells were in good condition and were not affected by the doses given.

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