Jokar Mohammad Hassan, Sedighi Sima, Moradzadeh Maliheh
Golestan Rheumatology Research Center, Sayad Shirazi Hospital, Golestan University of Medical Sciences, Gorgan, Iran.
Equal first author.
Avicenna J Phytomed. 2021 Jul-Aug;11(4):314-323. doi: 10.22038/AJP.2021.17604.
Acute promyelocytic leukemia (APL) is among the most threatening hematological malignant cancers. Defects in cell growth and apoptotic pathways lead to the pathogenesis of the disease as well as its resistance to therapy; therefore, it is a good model for examining pro-apoptotic agents. The present study compared the molecular mechanism induced by kaempferol and epigallocatechin gallate (EGCG) as well as all-trans retinoic acid (ATRA), in HL-60 leukemia cells during five days.
Cell viability was determined by resazurin assay following treatment with ATRA (10 µM), EGCG, and kaempferol (12.5-100 µM), and apoptosis was detected by the ANX V/PI kit. Moreover, the levels of genes involved in apoptosis (, , , , , , , , and ) and multi-drug resistance (MDR, and ) were assessed by using real-time PCR test.
Based on the findings, kaempferol decreased cell viability and increased apoptosis in HL60 cells more than EGCG. Apoptosis was induced via extrinsic and intrinsic pathways in HL60 cells by kaempferol and EGCG. In addition, kaempferol and EGCG increased apoptosis and inhibited MDR in a concentration- and time-dependent manner.
Kaempferol at high concentrations can be taken into consideration for treating patients with APL as compared with EGCG.
急性早幼粒细胞白血病（APL）是最具威胁性的血液系统恶性肿瘤之一。细胞生长和凋亡途径的缺陷导致了该疾病的发病机制及其对治疗的抗性；因此，它是研究促凋亡剂的良好模型。本研究比较了山奈酚、表没食子儿茶素没食子酸酯（EGCG）以及全反式维甲酸（ATRA）在五天内对HL-60白血病细胞诱导的分子机制。
用ATRA（10 µM）、EGCG和山奈酚（12.5 - 100 µM）处理后，通过刃天青测定法测定细胞活力，并用ANX V/PI试剂盒检测细胞凋亡。此外，通过实时PCR检测评估凋亡相关基因（、、、、、、、和）以及多药耐药相关基因（MDR、和）的水平。
基于研究结果，山奈酚比EGCG更能降低HL60细胞的活力并增加其凋亡。山奈酚和EGCG通过外源性和内源性途径诱导HL60细胞凋亡。此外，山奈酚和EGCG以浓度和时间依赖性方式增加细胞凋亡并抑制多药耐药。
与EGCG相比，高浓度的山奈酚可考虑用于治疗APL患者。
