Anti-BCL2L1 (full length) polyclonal antibody

Breast cancer is the second leading cause of death among women globally. The existing treatment options for breast cancer are largely associated with severe toxicities, and lower efficacies. Therefore, there is an urgent need for the development of non-toxic effective drugs against breast cancer. For this purpose, drug repositioning strategy was used to evaluate the anti-cancer potential of a library of heterocyclic drugs. The major advantage of drug repurposing is that the pharmacokinetic, pharmacodynamic, and toxicity profiles of drugs are well documented. In the current study, we screened 97 drugs of different chemical classes, and among them aripiprazole, an antipsychotic drug, was found to be sufficiently active against breast cancer cell line MCF-7. Aripiprazole showed a cytotoxicity (IC50= 12.1 +/- 0.40 mu M) to MCF-7 cells, comparable to the standard anticancer drug doxorubicin (IC50= 1.25 +/- 0.34 mu M). Aripiprazole was also found to be active against other cancer cell lines, including MDA-MB-231 (IC50= 19.83 +/- 0.27 mu M), AU565 (IC50= 18.02 +/- 0.44 mu M), and BT-474 (IC50= 36.42 +/- 0.12 mu M). Aripiprazole significantly inhibited the cell cycle progression at subG(0)G(1)phase, and enhanced apoptosis in MCF-7 breast cancer cells. The drug was also able to significantly increase the nuclear condensation, and modulated the expression of certain genes involved in breast cancer, such as caspases 3, and 9, BAK-1, C-MYC, BCL2L1, BCL-10, and BCL-2. Further studies are needed to explore the effect of aripiprazole on intrinsic and extrinsic pathways of apoptosis in cancer cells.

Nur77, encoded by Nr4a1 (alias Nur77), plays rotes in cell death, survival, and inflammation. To study the role of Nur77 in liver regeneration, wild-type (WT) and Nur77 knockout (KO) mice were subjected to standard two-thirds partial hepatectomy (PH). Nur77 mRNA and protein levels were markedly induced at 1 hour after PH in WT livers, coinciding with ERK1/2 activation. Surprisingly, Nur77 KO mice exhibited a higher liver-to-body weight ratio than WT mice at 24, 48, and 72 hours after PH. Nur77 KO livers exhibited increase in Ki-67-positive hepatocytes at 24 hours, with early induction of cell-cycle genes. Despite accelerated regeneration, Nur77 KO livers paradoxically incurred necrosis, hepatocyte apoptosis, elevated serum aLanine aminotransferase activity, and Kupffer cell accumulation. Microarray analysis revealed upregulation of genes modulating inflammation, cell proliferation, and apoptosis but down-regulation (due to Nur77 deficiency) of glucose and lipid homeostasis genes. Levels of proinflammatory cytokines IL-6, IL-12, IL-23, and CCL2 were increased and levels of anti-inflammatory IL-10 were decreased, compared with WT. Activated NF-B-kappa and STAT3 and mRNA levels of target genes Myc and Bcl2l1 were elevated in Nur77 KO livers. Overall, Nur77 appears essential for regulating early signaling of Liver regeneration by modulating cytokine-mediated inflammatory, apoptotic, and energy mobilization processes. The accelerated liver regeneration observed in Nur77 KO mice is Likely due to a compensatory effect caused by injury.