Paper Title
Apoptotic Effects of Bortezomiband Clotrimazole Combinations on Hl-60 Acute Myeloid Leukemic Cells

Abstract
Cancer is a common disaster worldwide so as its resistance to be coped with. Especially, leukemia is one of the most deadly cancers known. Although new researches to have got alternative treatments are still ongoing, only a few of them gets ahead. When it comes to compare for being alternate, there are some different drugs with regards to their likely dual pharmacological influence. One of them is an imidazole antifungal, clotrimazole, clinically used against fungal infections. Beyond its antifungal action, it seems that it may be antiproliferative versus certain cancer cells in terms of some in vitro studies.Given the importance of fungal infections seen in the cancer patients,it is urgent to take care of them by struggling both cancer and fungal infections. With regard to mentioned above, in this study, it was aimed to investigate following two drugs’ combination, effective anticancer drug bortezomib,a proteasome inhibitor, is one of effective FDA approved drugs clinically used recently for malignancy especially used so as to treat myelomas and certain leukemic cells and antifungal clotrimazole,on HL-60 myeloid leukemic cells. There were two different assays carried out. Cytotoxicity at 24th hour was assessed by using WST-1 method and apoptotic determination was carried out through the instrument of Annexin/PI staining kit. According to the results of repetitive WST-1 (4-[3-(4-Iodo-phenyl)-2-(4-nitrophenyl)-2H-5 tetrazolio]-1,3-benzene disulphonate) assays fulfilled three different times, subsequently, cell viability were calculated and. IC50 and IC25 values were calculated. Then,Annexin-V/PI binding assay was performed afterward by a flow cytometer. Apoptotic activities were analysed in HL-60 cells which were treated with bortezomib’s and clotrimazole’s and combined concentrations. In respect to the results,combination of drugs exhibited much more apoptotic effect than their own on HL-60 cells. By carrying out this study, on the one hand, it wasshown that jointlyusing of following combination, as an antifungal, clotrimazole, and as proteasome inhibitor, bortezomib, would be a promising antiproliferative and antiapoptotic drug combination in AML patients, yet on the other hand, owing toclotrimazole’s antifungal activity, that combination would be a worthwhile candidate in respect with struggling fungal infections usuallyseen in cancer patients. Keywords - Apoptosis, Bortezomib, Clotrimazole, Acute, Myeloid, Leukemia, HL-60