Activity of cyclin B1 in HL-60 cells treated with etoposide.
Cyclin B1 triggers G2/M phase transition phosphorylating with its catalytical partner - Cdc2 many of the molecular targets essential for cell cycle progression. Human leukemia cell line HL-60 were treated with increasing doses of etoposide (ETP) (0.5; 0.75; 1μM) to investigate how the drug affects cell morphology, viability, cell cycle distribution and expression of cyclin B1. To achieve this aim we applied light and transmission electron microscopy to observe morphological and ultra structural changes, image-based cytometry for apoptosis evaluation and cell cycle analysis, and then we conducted immunohistochemical and immunofluorescence staining to visualize cyclin localization and expression. Quantitive data about cyclin B1 expression were obtained from flow cytometry. Etoposide caused decrease in cell viability, induced apoptosis and G2/M arrest accompanied by enhanced expression of cyclin B1. Changes in expression and localization of cyclin B1 may constitute a part of the mechanism responsible for resistance of HL-60 cells to etoposide. Our results may reflect involvement of cyclin B1 in opposite processes - apoptosis induction and maintenance of cell viability in leukemia cells. We hypothesized possible roles and pathways by which cyclin B1 takes part in drug treatment response and chemosensitivity.
Department of Histology and Embryology, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Karłowicza 24, 85-092 Bydgoszcz, Poland.
Agnieszka
A
Żuryń
Department of Histology and Embryology, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Karłowicza 24, 85-092 Bydgoszcz, Poland.
Adrian
A
Krajewski
Department of Histology and Embryology, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Karłowicza 24, 85-092 Bydgoszcz, Poland.
Dawid
D
Szulc
Plant Breeding and Acclimatization Institute - National Research Institute, Bydgoszcz Research Center, Department of Genetics and Breeding of Root Crops, Laboratory of Biotechnology, Powstańców Wielkopolskich 10, 85-090 Bydgoszcz, Poland.
Anna
A
Litwiniec
Department of Histology and Embryology, Faculty of Medicine, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Karłowicza 24, 85-092 Bydgoszcz, Poland. Electronic address: agrzanka@cm.umk.pl.
Alina
A
Grzanka
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056744:Cyclin B1 / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans
D000972:Antineoplastic Agents, Phytogenic; C534699:CCNB1 protein, human; D056744:Cyclin B1; D005047:Etoposide
Cell cycle; Cell death; Chemoresistance; Cyclin B1; Etoposide; HL-60