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首页> 外文期刊>Current therapeutic research, clinical and experimental. >Effects of griseofulvin on apoptosis through caspase-3- and caspase-9-dependent pathways in K562 leukemia cells: An in vitro study
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Effects of griseofulvin on apoptosis through caspase-3- and caspase-9-dependent pathways in K562 leukemia cells: An in vitro study

机译：灰黄霉素通过caspase-3和caspase-9依赖性途径对K562白血病细胞凋亡的影响：体外研究

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Background: Griseofulvin, an oral nontoxic antifungal drug, has been reported to possess anticancer effect in human cancer cells, while the mechanisms are not completely understood. Objective: The aim of this study was to investigate the cytotoxic effect of griseofulvin on K562 cells and to understand its underlying molecular pathways. Methods: K562 cells were treated with griseofulvin at different concentrations for 24 hours, and the inhibition effect of griseofulvin on K562 cell proliferation was assessed by tetrazolium salt colorimetric assay. Apoptosis was assessed by examining nuclear morphology and quantifying phosphatidylserine externalization, and alterations in cellular morphology were analyzed by laser scanning confocal microscopy for fluorescent analysis. Flow cytometry was used in the analysis of cell cycle, mitochondrial membrane potential, and caspase pathways. Results: Griseofulvin could inhibit the growth of K562 cells in a dose-dependent manner with a mean (SD) inhibitory concentration of 50% value of 15.38 (1.35) μg/mL compared with untreated controls. Apoptosis was induced in K562 cells (38.35% [2.73%]; P < 0.01) by griseofulvin with the observation of both an increase in phosphatidylserine level and accumulation of chromatin nucleation in griseofulvintreated cells. In addition, cell-cycle analysis using propidium iodide staining suggested a significant G2/M accumulation (increase from mean 17.64% [4.49%] to 48.29 [1.89%]; P < 0.01) as a result of griseofulvin treatment. Flow cytometry analysis found that griseofulvin treatment was associated with the depolarization of the mitochondrial membrane in K562 cells. Furthermore, increased activities of caspase-3 by 22.15-fold (P < 0.01) and caspase-9 by 16.73-fold (P < 0.01) were observed in K562 cells after griseofulvin treatment compared with the untreated control; a decrease of caspase-8 activity was also observed, but the change was not statistically significant. Conclusions: These findings suggest that griseofulvin inhibited growth of K562 cells and induced cell apoptosis through cell-cycle arrest and mitochondrial membrane potential decrease as well as caspase-3 and -9 activation. Further testing is needed to evaluate the potential of griseofulvin as a candidate in the chemotherapy of hematologic malignancies.
机译：背景：灰黄霉素（Griseofulvin）是一种口服无毒抗真菌药物，据报道在人类癌细胞中具有抗癌作用，但其机理尚不完全清楚。目的：本研究的目的是研究灰黄霉素对K562细胞的细胞毒性作用，并了解其潜在的分子途径。方法：用不同浓度的灰黄霉素处理K562细胞24小时，用四唑盐比色法评价灰黄霉素对K562细胞增殖的抑制作用。通过检查核形态并定量磷脂酰丝氨酸外在化来评估细胞凋亡，并通过激光扫描共聚焦显微镜分析细胞形态的变化以进行荧光分析。流式细胞仪用于细胞周期，线粒体膜电位和半胱天冬酶途径的分析。结果：灰黄霉素可以剂量依赖性方式抑制K562细胞的生长，与未处理的对照组相比，平均（SD）抑制浓度为50％的15.38（1.35）μg/ mL。灰黄霉素诱导了K562细胞的凋亡（38.35％[2.73％]; P <0.01），同时观察到磷脂酰丝氨酸水平的增加和染色质黄嘌呤处理细胞中染色质成核的积累。此外，使用碘化丙锭染色的细胞周期分析表明，由于灰黄霉素的处理，G2 / M积累显着（从平均17.64％[4.49％]增加到48.29 [1.89％]; P <0.01）。流式细胞仪分析发现灰黄霉素治疗与K562细胞线粒体膜的去极化有关。此外，在灰黄霉素治疗后的K562细胞中，与未处理的对照组相比，caspase-3的活性增加了22.15倍（P <0.01），caspase-9的活性增加了16.73倍（P <0.01）。也观察到胱天蛋白酶8活性降低，但是该变化在统计学上不显着。结论：这些发现表明灰黄霉素可以抑制K562细胞的生长，并通过细胞周期停滞和线粒体膜电位降低以及caspase-3和-9激活而诱导细胞凋亡。需要进一步测试以评估灰黄霉素在血液系统恶性肿瘤化疗中的潜力。

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