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