The treatment of triple-negative breast cancer (TNBC) remains a major challenge. The present study aimed to throw more light on the role of copper (I)-nicotinate complex (CNC) as an antitumor as well as a proapoptotic agent. In this study, the HCC-1806 cell line was used as a model for TNBC. Cell cycle, apoptosis assay, and programmed cell death protein-1 were investigated by flowcytometry. Besides, the comet assay was performed using a fluorescence microscope. The enzyme-linked immunosorbent assay technique was used for the detection of phospho-Chk1 at ser 317 and caspase-3. Moreover, the gene expression of survivin was identified by real-time polymerase chain reaction.Finally, superoxide dismutase (SOD) was calorimetrically assayed. The viability of HCC-1806 cells treated with CNC was decreased in a dose-dependent manner. The tendency for apoptotic machinery was observed through the increase in the sub G0 peak, the percentage of early and late apoptotic phases, and the elevation in caspase-3 levels associated with a downregulation of the survivin gene expression. The antioxidant property of the complex, reflected by elevated SOD activity, may contribute to mediate the cell death pathways. Low concentrations of CNC were found to favor the apoptotis-mediated mechanism. However, one cannot neglect the abundance of cell necrosis-mediated death of cells via CNC, especially at higher concentrations.

Carbon tetrachloride (CCl4) is a known ecological hazardous xenobiotic that could motivate hepatotoxicity. We aimed to examine, for the first time, the therapeutic potential of nickel(II) diacetyl monoxime-2-pyridyl hydrazone complex versus CCl4induced hepatotoxicity in rats. We used six rat groups of ten animals each. The negative control, vehicle, normal rats injected i.p. with the complex (2.4 mg/kg/day), positive control rats injected i.p. with CCl4, and treated rats administered complex via injection at low and high concentrations of 1.2 and 2.4 mg/kg/day, respectively at the same time as CCl4 injection for shortterm (3-weeks) and long-term (8-weeks) treatment. Intoxicated-rodents exhibited significant elevations in the liver index, hepatic serum markers, and oxidative stress with significant reductions in the hepatic, antioxidants, nucleic acids, and proteins. Complex co-treatment with CCl4 significantly suppressed the elevated liver enzyme activities, attenuated oxidative stress, reactivated antioxidant-system components, and amended the hepatic tissue injury. The complex high dose was more efficient than the low dose. Results of negative control were analogous to those of normal rats injected with the complex high dose. The histopathological analysis also supported the above findings. These results show that complex has good antioxidant and therapeutic properties, which can help in treating and preventing CCl4-induced hepatotoxicity.

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Hepatocellular carcinoma (HCC) is one of the most common types of cancer and its high mortality and short survival time causes a serious worldwide health burden. Chemotherapy as 5-Flourouracil (5-FU) is used as the first-choice treatment for HCC, however it is associated with resistance, low efficacy and has side effects. Consequently, the administration of mesenchymal stem cells (MSCs) as a novel therapy for HCC holds great promise. MSCs can differentiate into hepatocytes, reduce liver inflammation, promote hepatic regeneration and secrete protective cytokines. This is the first study that sheds new light on the role of MSCs alone or together with 5-FU in HCC. In this study, Bone marrow derived-MSCs were prepared and HCC model was induced via treating rats with Ndiethylnitrosamine (DEN). The effect of treatments was evaluated by biochemical, tumor markers, macroscopical, and histopathological analysis. Also, cell cycle, apoptosis assay, KI67 and CD95 were performed by Flowcytometry. The administration of MSCs together with 5-FU yields a decrease in the liver enzymes with down-regulation of tumor markers as well as improvement of histopathological picture. In addition, such treatment decreased cell proliferation that associated with the down-regulation of KI67 expression. Furthermore, MSCs did not mediate the apoptosis pathway together with reduction of CD95 expression and cell cycle arrest at G0/G1 phase. In conclusion, MSCs exerted antitumor effects by inhibiting proliferation, modulating the cell cycle in G0/G1 phase and improved the toxic effect of 5FU via improvement of liver enzymes and decreased tumor markers.