Asgari Fatemeh, Mahinpour Roya, Moradi Leila, Haghighipour Nooshin
Department of Cellular and Molecular Biology, Faculty of Chemistry, University of Kashan, P.O.Box 8731753153, Kashan, Iran.
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, P.O.Box 8731753153, Kashan, Iran.
J Cell Commun Signal. 2020 Mar;14(1):77-91. doi: 10.1007/s12079-019-00530-w. Epub 2019 Sep 6.
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.
慢性髓性白血病（CML）是一种伴有特定染色体畸变的恶性血液病，是白血病的常见形式。色烯家族具有强大的抗癌作用。因此，研究了二氢吡喃并[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作用，并与正常外周血单个核细胞（PBMC）进行了比较。将K562细胞在上述色烯衍生物存在下，浓度为40至200μM培养24至72小时。通过MTT法研究这些化合物对K562细胞系和PBMC生长和活力的影响。此外，使用流式细胞术研究凋亡诱导情况。在将K562细胞和PBMC暴露于4 - Clpgc 48小时后，使用实时PCR对BCL2、Bax、TP53和BCR - ABL基因进行相对定量。根据结果，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值分别为102±1.6μM和143±9.41μM，而pgc是最弱的，在K562细胞和PBMC中（72小时后）的IC50水平分别为278±2.7μM和366±47μM。结果表明，处理48小时后，K562细胞和PBMC对照组的凋亡细胞百分比分别从6.09％增加到84.10％和从17.2％增加到20.06％。此外，4 - Clpgc处理使K562细胞中Bax和TP53基因的表达分别增加42.74倍和35.88倍，在PBMC中分别增加9.60倍和7.75倍。另一方面，K562细胞和PBMC中BCL2的表达分别降低了1.47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，这些衍生物可被视为白血病治疗的合适候选药物。
