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Molecular mechanisms of apoptosis induction in K562 and KG1a leukemia cells by a water-soluble copper(II) thiosemicarbazone complex.
JBIC Journal of Biological Inorganic Chemistry ( IF 2.7 ) Pub Date : 2020-04-09 , DOI: 10.1007/s00775-020-01769-0 Fatemeh Ghorbani Parsa 1 , Mohammad Ali Hosseinpour Feizi 1 , Reza Safaralizadeh 1 , Seyed Abolfazl Hosseini-Yazdi 2 , Majid Mahdavi 1
中文翻译:
水溶性铜(II)硫代半碳zone复合物诱导K562和KG1a白血病细胞凋亡的分子机制。
更新日期:2020-04-09
JBIC Journal of Biological Inorganic Chemistry ( IF 2.7 ) Pub Date : 2020-04-09 , DOI: 10.1007/s00775-020-01769-0 Fatemeh Ghorbani Parsa 1 , Mohammad Ali Hosseinpour Feizi 1 , Reza Safaralizadeh 1 , Seyed Abolfazl Hosseini-Yazdi 2 , Majid Mahdavi 1
Affiliation
Abstract
Thiosemicarbazones (TSCs) and their metal complexes exhibit pronounced and selective cytotoxic potential against a broad span of cancers. Here, we assessed the anti-cancer activity of a water-soluble copper(II) complex of thiosemicarbazone (Cu-TSC) against two cancer cell lines of human leukemia. Our analysis revealed that Cu-TSC treatment results in a time and dose-dependent growth inhibition in K562 and KG1a cells while sparing normal human fibroblast (HFF2) cells. The IC50 values for the Cu-TSC treatment were measured to be 21.7 ± 1.5 µM and 50.25 ± 2.5 µM for K562 and KG1a cells, respectively. Cell cycle analysis indicated that Cu-TSC induces the accumulation of cells in the sub-G1 fraction as well as the reversible arrest in G0/G1 and G2/M phases in K562 and KG1a cells, respectively. Furthermore, the occurrence of apoptosis as the prime mode of cell death was verified through apoptotic body formation, phosphatidylserine externalization, and caspase-3 activation. Additionally, the real-time quantitative PCR analysis revealed that Cu-TSC triggers apoptosis in both cell lines via the upregulation of caspases-8, -9, and the changing of Bax/Bcl2 ratio. Finally, flow cytometric analysis confirmed that Cu-TSC treatment causes the enhancement of reactive oxygen species formation in both K562 and KG1a cells. Altogether, these findings suggest that Cu-TSC is a promising inducer of apoptosis in leukemia cells and carries potential as an anti-cancer compound.Graphic abstract
中文翻译:
水溶性铜(II)硫代半碳zone复合物诱导K562和KG1a白血病细胞凋亡的分子机制。