Determination of apoptosis and changes on cell cycle genes expressions in HL60 cell line induced with bendamustine

Purpose:acute myeloid leukemia (aml), is a heterogeneous clonal disorder of hematopoietic progenitor cells. acute promyelocytic leukemia (apl), is a subtype of aml and characterized by aberrant morphology of promyelocytes. the most specific chromosomal disorder that occurs in apl patients is (15;17) translocation. this translocation the promyelocytic leukemia (pml) gene on chromosome 15 and the retinoic acid receptor (rar) alpha gene on chromosome 17 fuse and produce a pml-rarα fusion protein. bendamustine is a water soluble, white, microcrystalline powder with amphoteric properties due to a nitrogen mustard group and a butyric acid side chain. bendamustine acts as an alkylating agent and also has purine analog activity. bendamustine has more moderate toxicity profile than the other alkylatingg agents. in our study, it is aimed to investigate cytotoxic, cytostatic and apoptotic effects of bendamustine on apl cell line hl60. also we aime to evaluate the effect of bendamustine on hl60 cells according to the expression of genes including several signal transduction pathways such as; cell cycle, mitotic catastrophe and apoptosis, materials and methods: cytotoxic effect of bendamustine on hl60 cell line was assessed by wst-1 assay, apoptotic effect by annexin v and apodirect tunnel assay and cytostatic effect by cycletest plus dna reagent kit. also the effect of bendamustine on expression levels of several cell cycle, mitotic catastrophe and apoptosis related genes in hl60 was determined by quantitative rt-pcr relatively. results: we determined that bendamustine has cytotoxic effect on hl60 cell line with high-dose treatment. also we found that bendamustine significantly induces apoptosis in dose dependent manner and has no cytostatic effects on hl60 cells. after the 48 hours treatment with bendamustine, expression levels of apoptosis related casp7, casp8, casp9 genes were upregulated 2.4, 5.7, 6.8 fold in hl60 cells, relatively. also expressions of mitotic catastrophe related genes plk1downregulated 2.5 fold and plk2 which as known as tumor suppressor gene, upregulated 17 fold. conclusion: our data suggest that bendamustine is effective on cell death mechanisms such as apoptosis ve mitotic catastrophe and can be used in supplement as a alternative treatment.