The effect of cordycepine on HIF1a-mediated proliferation and viability in chronic myeloid leukemia cells

Abstract

Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a myeloproliferative disorder characterized by increased proliferation of granulocyte cell lines without losing their capacity to differentiate. With improvement in survival and increase in prevalence of CML, it seems critical to find cost effective and more safe and available treatment strategies. Through this, cordycepin is a material with various treatment effects including anti cancer effect. through studies it can have treatment applications by different mechanisms in different types of leukemias. A focal point of the cell's adaptation to hypoxia is the transcription factor HIF1α (hypoxia-inducible factor 1 alpha), which affects the expression of specific gene networks involved in cellular energetics and metabolism.HIF1α-induced metabolic adaptation promotes angiogenesis, participates in the escape from immune recognition, and increases cancer cell antioxidant capacity. Various studies have shown that increasing HIF-1a expression enhances the proliferation of cancer cells in CML by increasing p21 expression and downregulating miR-20a. The aim of this study was to investigate the expression of these genes after treatment with cordycepin. Material and Methods: In this study, K562 cells as a common CML cell line were treated with IC50 concentration of cordycepine under both hypoxic and normoxic conditions for 24 hours and then total RNA was extracted from them. After cDNA synthesis, the expression levels of HIF-1a and p21 as well as the mir-20a are quantitatively determined by real-time PCR. Results: In this study, by using qRT-PCR test, changes in expression of HIF-1a, p21 and miR-20a after treatment with cordycepin was shown in which p21 had significant decreased expression and miR-20a had significant increased expression, but there was’nt any significant change in HIF-1a expression