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The chromene derivative 4-Clpgc inhibits cell proliferation and induces apoptosis in the K562 cell line.
Journal of Cell Communication and Signaling ( IF 4.1 ) Pub Date : 2019-09-06 , DOI: 10.1007/s12079-019-00530-w
Fatemeh Asgari 1 , Roya Mahinpour 1 , Leila Moradi 2 , Nooshin Haghighipour 3
Affiliation  

Chronic myeloid leukemia (CML) is a malignant blood disease with a particular chromosomal aberration that is known as a common form of leukemia. The chromene family exhibits strong anti-cancer effects. Therefore, the effects of six members of the dihydropyrano [2,3-g] chromene family on cell toxicity and apoptosis induction in K562 cancer cells were investigated and compared with those of normal peripheral blood mononuclear cells (PBMCs). The K562 cells were cultured in the presence of the aforementioned chromene derivatives at concentrations of 40 to 200 μM for 24 to 72 h. The effects of these compounds on the growth and viability of the K562 cell line and PBMCs were studied through MTT assay. Furthermore, apoptosis induction was investigated using flow cytometry. Real-time PCR was used for relative quantification of BCL2, Bax, TP53 and BCR- ABL genes after 48 h of exposing K562 cells and PBMCs to 4-Clpgc. Based on the results, these chromene derivatives inhibited the growth of K562 cells. According to the obtained data, 4-Clpgc was the strongest compound with IC50 values of 102 ± 1.6 μM and 143 ± 9.41 μM in K562 cells and PBMCs, while pgc was the weakest one with IC50 levels of 278 ± 2.7 μM and 366 ± 47 μM in K562 cells and PBMCs (after 72 h), respectively. The results demonstrated that the apoptotic cell percentage in the control group increased from 6.09% to 84.10% and 17.2% to 20.06% in K562 cells and PBMCs after 48 h of treatment, respectively. Moreover, 4-Clpgc treatment increased the expression of Bax and TP53 genes by 42.74 and 35.88 folds in K562 cells and 9.60 and 7.75 folds in PBMCs, respectively. On the other hand, the expression of BCL2 was reduced by 1.47 and 1.38 folds in K562 cells and PBMCs, respectively. These compounds were associated with less toxic effects on normal cells, compared to the cancer cells. In conclusion, these derivatives can be considered as appropriate candidates for leukemia treatment.

中文翻译:

色烯衍生物4-Clpgc在K562细胞系中抑制细胞增殖并诱导细胞凋亡。

慢性粒细胞白血病(CML)是一种恶性血液病,具有特定的染色体畸变,被称为白血病的常见形式。色烯家族具有很强的抗癌作用。因此,研究了六氢吡喃并[2,3-g]色烯家族的六个成员对K562癌细胞的细胞毒性和凋亡诱导的影响,并将其与正常外周血单个核细胞(PBMC)进行了比较。在上述色烯衍生物的存在下,以40至200μM的浓度将K562细胞培养24至72小时。通过MTT分析研究了这些化合物对K562细胞系和PBMCs的生长和活力的影响。此外,使用流式细胞仪研究了凋亡诱导。实时荧光定量PCR用于BCL2,Bax,将K562细胞和PBMC暴露于4-Clpgc 48小时后的TP53和BCR-ABL基因。基于这些结果,这些色烯衍生物抑制了K562细胞的生长。根据获得的数据,4-Clpgc是最强的化合物,在K562细胞和PBMC中的IC50值为102±1.6μM和143±9.41μM,而pgc是最弱的化合物,IC50值为278±2.7μM和366±47在K562细胞和PBMC中分别为μM(72小时后)。结果表明,处理48小时后,对照组的K562细胞和PBMC的凋亡细胞百分比分别从6.09%增加到84.10%,从17.2%增加到20.06%。此外,4-Clpgc处理在K562细胞中使Bax和TP53基因的表达分别增加42.74和35.88倍,而在PBMC中使其增加9.60和7.75倍。另一方面,BCL2的表达减少了1。在K562细胞和PBMC中分别达到47倍和1.38倍。与癌细胞相比,这些化合物对正常细胞的毒性作用较小。总之,这些衍生物可以被认为是白血病治疗的合适候选者。
更新日期:2019-09-06
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