A Benzylideneacetophenone Derivative Induces Apoptosis of Radiation-Resistant Human Breast Cancer Cells via Oxidative Stress

Benzylideneacetophenone derivative (1E)-1-(4-hydroxy-3-methoxyphenyl) hept-1-en-3-one (JC3) elicited cytotoxic effects on MDA-MB 231 human breast cancer cells-radiation resistant cells (MDA-MB 231-RR), in a dose-dependent manner, with an IC₅₀ value of 6 μM JC3. JC3-mediated apoptosis was confirmed by increase in sub-G1 cell population. JC3 disrupted the mitochondrial membrane potential, and reduced expression of anti-apoptotic B cell lymphoma-2 protein, whereas it increased expression of pro-apoptotic Bcl-2-associated X protein, leading to the cleavage of caspase-9, caspase-3 and poly (ADP-ribose) polymerase. In addition, JC3 activated mitogen-activated protein kinases, and specific inhibitors of these kinases abrogated the JC3-induced increase in apoptotic bodies. JC3 increased the level of intracellular reactive oxygen species and enhanced oxidative macromolecular damage via lipid peroxidation, protein carbonylation, and DNA strand breakage. Considering these findings, JC3 is an effective therapy against radiation-resistant human breast cancer cells.

A Pig to Canine Auxiliary Hepatic Xenotransplantation Model: Prevention of Hyperacute Rejection via Blocking the Kupffer Cells and Regulating the Complement Family

PURPOSE: We designed a pig to canine liver xenotransplantation model to study the diverse immunologic and hemodynamic consequences that follow xenotransplantation and hyperacute rejection. METHODS: The animals were divided into two groups: the cobra venom factor and Gadolinium chloride treatment group (CVF+Gd group) (3 cases) and the control group (3 cases). The donor pig's whole liver was harvested, and then the harvested pig's whole liver was transplanted into a dog after the dog underwent left hepatectomy. After reperfusion of the graft, blood samples were taken 20, 40 and 60 minutes after reperfusion, and the liver, lung and kidney tissues were taken 1 hour after reperfusion. RESULTS: In the control group, the grafts showed a patchy hypoperfused liver surface and it felt rubbery solid compared to the CVF+Gd group. The serum total protein, albumin, fibrinogen and platelets decreased abruptly and there were no significant differences between the two groups. The serum PT, PTT and FDP were increased in both groups and the CVF+Gd group showed a more obtuse slope than the control group. We could not find any intravascular pathologic changes on the microscopic findings of the graft. Only scant intravascular fibrin deposition was found. Hepatocellular vacuolization and sinusoidal dilatation were also found. There were patches of necrosis without any zonal distribution, intrasinusoidal neutrophil sequestration and interstitial hemorrhage. These findings were milder in the CVF+Gd group. CONCLUSION: The pig to canine partial auxiliary liver xenotransplantation model is feasible and it is a good model before starting to perform pig to primate liver xenotransplantation. In the CVF+Gd group, pathologic findings like patch hepatocyte necrosis etc. were less severe. As there were no corresponding vascular pathologic findings, these findings are not the direct effect of CVF and gadolinium treatment, and so other factors like Ischemia- reperfusion injury should be considered.