Cytoskeletal reorganization and cell death in mitoxantrone-treated lung cancer cells.
The aim of this study was to investigate the cytotoxic effect of mitoxantrone on two human non-small cell lung cancer cell lines, A549 (p53+) and H1299 (p53-). To our knowledge, this is the first study to evaluate the impact of MXT on the organization of cytoskeletal proteins. Analyses were performed using fluorescence and transmission electron microscopy, spectrophotometric techniques, flow cytometry and Western blotting. It was shown that H1299 cells are significantly more sensitive to mitoxantrone than the A549 cell line, and that the growth-inhibitory effect of the drug is dose-dependent only after longer incubation. The observed presence of ring-like microtubule structures and mitochondria surrounding the nuclei of H1299 cells could be a manifestation of increased tubulin polymerization requiring large amounts of energy, whereas the loss of actin stress fibers was presumably not the cause but rather the consequence of cell death induction. Treatment with mitoxantrone also led to the appearance of structures resembling agresomes in H1299 cells and to nucleolar segregation in both cell lines. It was demonstrated that cells arrested in the S phase were most susceptible to cell death induction, and that triggered intracellular changes led mainly to apoptosis. High concentrations induced necrosis and some H1299 cells exhibited morphological features of mitotic catastrophe.
Department of Histology and Embryology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Karlowicza 24, 85-092 Bydgoszcz, Poland. Electronic address: apawlik@onet.eu.
Andrzej
A
Pawlik
Department of Histology and Embryology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Karlowicza 24, 85-092 Bydgoszcz, Poland. Electronic address: m.szczepanski1@gmail.com.
Mariusz Andrzej
MA
Szczepanski
Department of Histology and Embryology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Karlowicza 24, 85-092 Bydgoszcz, Poland. Electronic address: ania.klimaszewska@op.pl.
Anna
A
Klimaszewska-Wisniewska
Department of Immunology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, M. Curie Sklodowskiej 9, 85-094 Bydgoszcz, Poland. Electronic address: lidiagackowska@gmail.com.
Lidia
L
Gackowska
Department of Histology and Embryology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Karlowicza 24, 85-092 Bydgoszcz, Poland. Electronic address: azuryn@cm.umk.pl.
Agnieszka
A
Zuryn
Department of Histology and Embryology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Karlowicza 24, 85-092 Bydgoszcz, Poland. Electronic address: agrzanka@cm.umk.pl.
Alina
A
Grzanka
D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D008942:Mitoxantrone / Q000494:pharmacology*
D008942:Mitoxantrone
Apoptosis; Cell death; Cytoskeleton; Lung cancer; Mitoxantrone; Tubulin