A benzimidazolium salt induces apoptosis and arrests cells at sub-G1 phase in epithelial ovarian cancer cells.

BACKGROUND: Ovarian cancer, also known as a silent killer, is the deadliest gynecological cancer in women worldwide. Epithelial ovarian cancers constitute the majority of ovarian cancers, and diagnosis can be made in advanced stages, which greatly reduces the likelihood of treatment and lowers the survival rate. For the treatment of epithelial ovarian cancers, the search for synthetic agents as well as agents of natural origin continues. The effects of 1-(2-cyanobenzyl)-3-(4-vinylbenzyl)-1H-benzo[d]imidazole-3-ium chloride (BD), a benzimidazole derivative, were investigated on epithelial ovarian cancer cells. METHODS AND RESULTS: In our study, the effects of BD on proliferation, colony formation, cell death by apoptosis and the cell cycle in A2780 and A2780 Adriamycin (ADR) ovarian cancer cell lines were investigated. Proliferation was examined with cell viability analysis, colony formation and apoptosis with Annexin V staining and cell cycle analyses with PI staining, respectively. As a result of the analyses, BD inhibited cell proliferation and colony formation, induced apoptosis and cell death at 48 h in A2780 and A2780 ADR cells at 10.10 and 10.36 µM concentrations, respectively. In addition, A2780 and A2780ADR cells were arrested in the Sub-G1 phase of the cell cycle. CONCLUSIONS: BD suppresses cancer cell progression by showing antiproliferative effects on ovarian cancer cells. Further analyses are required to determine the mechanism of action of this agent and to demonstrate its potential as a suitable candidate for the treatment of epithelial ovarian cancer.

Effect of humanine on the Notch signaling pathway in myocardial infarction.

Background/aim: By applying humanin (HN) before myocardial infarction (MI), its protection in myocardial injury and the possible roles of its cellular mechanism in the Notch pathway were investigated. Materials and methods: The study was carried out at Firat University Experimental Research Center (12/24/2018-12/23/2019). Spraque-Dawley rats were divided into 10 groups: I (control) (n = 6), II (HN 6 h) (n = 6), III (HN 24 h) (n = 6), IV (HN day 7) (n = 6), V (MI 6 h) (n = 7), VI (MI 24 h) (n = 7), VII (MI day 7) (n = 7), VIII (MI+HN 6 h) (n = 7), IX (MI+HN 24 h) (n = 7), and X (MI+HN day 7) (n = 7). To create MI, 200 mg/kg of isoproterenol (ISO) was administered to the rats subcutaneously. Moreover, 252 µg/kg of HN was given intraperitoneally (ip) to the rats on its own and before MI. Molecular parameters Notch1, Notch2, Hes1, Hes2, Jagged1, Jagged2, DLL1, and DLL4 were examined using polymerase chain reaction in the heart tissue, Notch1, Hes1, and DLL4 were examined using western blot, while heart tissue was taken for histochemical examinations. Results: The mRNA expression levels of the Notch signaling members (Notch1, Notch2, Hes1, Hes2, Jagged1, Jagged2, DLL1, and DLL4) tended to decrease after MI. The Notch signaling members increased more significantly, especially toward day 7 after HN application before MI. In the western blot anylyses, the Notch1, Hes1, and DLL4 protein levels increased significantly toward day 7 in the groups given HN before MI. Moreover, the serum AST, LDH, CK-MB, and troponin I levels tended to decrease with the application of HN before MI and there was a significant decrease in edema, hemorrhage, and mononuclear cells in the heart tissue at 24 h post-MI and fibrosis on day 7 post-MI. Conclusion: HN administration before MI has a cardioprotective effect on rats via the Notch signaling pathway.