Department of Immunology, Division of Hematology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Medical Genetic, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Anticancer Agents Med Chem. 2019;19(12):1523-1534. doi: 10.2174/1871520619666190729150442.
Chronic Myeloid Leukaemia (CML) starts in certain blood-forming cells of the bone marrow when cells acquire Philadelphia chromosome. Nowadays, scientists attempt to find novel and safe therapeutic agents and approaches for CML therapy using Tyrosine Kinase Inhibitors (TKIs), CML conventional treatment agents, has some restrictions and also adverse effects. Recently, it has been proposed that phytochemicals, such as flavonoids due to their low side effects and notable safety have the potential to be used for CML therapy.
K-562 cells were exposed with three concentrations of the querectin (10, 40 and 80µM) for 12, 24 and 48 hours. After that, these cells apoptosis rate was estimated using Annexin-V/PI staining and flowcytometry analysis, and their proliferation rate was evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT). Finally, the expression of the 70 and 90 kilodalton heat shock proteins (HSP70 and 90), methionine adenosyltransferase 2A (MAT2A), Forkhead box protein M1 (FOXM1), caspase-3 and -8, Bcl-X(L) and Bax involved in leukemic cells survival and proliferation was assessed using Real-Time PCR within 12, 24 and 48 hours after exposure with quercetin 40 and 80µM.
Considering consequences, querecetin induced apoptosis in K-562 cells, and also abrogated these cells proliferation. On the other hand, RT-PCR results showed a reduction in some of the candidate genes expression, especially HSP70, Bcl-X(L) and FOXM1, when cells were treated with quercetin 40 and 80µM. Also, Bax, caspase-3 and caspase-8 expression was significantly improved in K-562 cells upon quercetin exposure.
We concluded that CML therapy by querecetin due to its anti-proliferative and anti-survival potentials could lead to the promising therapeutic outcome through targeting major survival and proliferation involved genes expression.
慢性髓性白血病（CML）始于骨髓中某些造血细胞获得费城染色体时。如今，科学家们试图使用酪氨酸激酶抑制剂（TKI）寻找新的、安全的治疗药物和方法来治疗 CML，CML 的常规治疗药物有一些局限性，也有不良反应。最近，有人提出，类黄酮等植物化学物质由于其副作用低、安全性显著，有可能用于治疗 CML。
用三种浓度的槲皮素（10、40 和 80µM）处理 K-562 细胞 12、24 和 48 小时。之后，通过 Annexin-V/PI 染色和流式细胞术分析评估这些细胞的凋亡率，并使用 3-[4,5-二甲基噻唑-2-基]-2,5 二苯基四唑溴盐（MTT）评估其增殖率。最后，在暴露于 40 和 80µM 槲皮素 12、24 和 48 小时后，使用实时 PCR 评估参与白血病细胞存活和增殖的 70 和 90 千道尔顿热休克蛋白（HSP70 和 90）、甲硫氨酸腺苷转移酶 2A（MAT2A）、叉头框蛋白 M1（FOXM1）、caspase-3 和 -8、Bcl-X（L）和 Bax 的表达。
考虑到后果，槲皮素诱导 K-562 细胞凋亡，并抑制其增殖。另一方面，RT-PCR 结果表明，当细胞用 40 和 80µM 槲皮素处理时，一些候选基因的表达减少，特别是 HSP70、Bcl-X（L）和 FOXM1。此外，槲皮素处理后 K-562 细胞中 Bax、caspase-3 和 caspase-8 的表达显著提高。
我们得出结论，槲皮素通过其抗增殖和抗生存潜力治疗 CML，可能通过靶向主要的生存和增殖相关基因表达，带来有希望的治疗效果。
