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- Title
Molecular mechanisms of apoptosis induction in K562 and KG1a leukemia cells by a water-soluble copper(II) thiosemicarbazone complex.
- Authors
Parsa, Fatemeh Ghorbani; Feizi, Mohammad Ali Hosseinpour; Safaralizadeh, Reza; Hosseini-Yazdi, Seyed Abolfazl; Mahdavi, Majid
- 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.
- Subjects
CELL analysis; APOPTOTIC bodies; CELL death; LEUKEMIA; CANCER cells; CELL cycle; APOPTOSIS
- Publication
Journal of Biological Inorganic Chemistry (JBIC), 2020, Vol 25, Issue 3, p383
- ISSN
0949-8257
- Publication type
Article
- DOI
10.1007/s00775-020-01769-0