OBJECTIVES: Flubendazole (FLU), a member of benzimidazole family of anthelmintic drugs, is able to inhibit proliferation of various cancer cells. The aim of present study was to elucidate the mechanisms of antiproliferative effect of FLU on colorectal cancer cells in vitro. METHODS: The effect of FLU on proliferation, microtubular network, DNA content, caspase activation and senescence induction was studied in SW480 and SW620 cell lines. KEY FINDINGS: Flubendazole significantly affected cell proliferation in a pattern typical for mitotic inhibitor. This was accompanied by decrease in cyclin D1 levels, increase in cyclin B1 levels, activation of caspase 2 and caspase 3/7 and PARP cleavage. Morphological observations revealed disruption of microtubular network, irregular mitotic spindles, formation of giant multinucleated cells and increase in nuclear area and DNA content. In SW620 cell line, 37.5% giant multinucleated cells induced by FLU treatment showed positivity for SA-β-galactosidase staining. Cell lines were able to recover from the treatment and this process was faster in SW480 cells. CONCLUSION: Flubendazole in low concentration temporarily inhibits cell proliferation and induces mitotic catastrophe and premature senescence in human colon cancer cells in vitro.
- Klíčová slova
- benzimidazoles, colorectal cancer cells, flubendazole, mitotic catastrophe, senescence,
- MeSH
- aparát dělícího vřeténka účinky léků ultrastruktura MeSH
- lidé MeSH
- mebendazol analogy a deriváty farmakologie MeSH
- mikrotubuly účinky léků ultrastruktura MeSH
- mitóza účinky léků MeSH
- nádorové buněčné linie MeSH
- obrovské buňky účinky léků ultrastruktura MeSH
- proliferace buněk účinky léků MeSH
- stárnutí buněk účinky léků MeSH
- tubulin metabolismus MeSH
- velikost buněčného jádra účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- flubendazole MeSH Prohlížeč
- mebendazol MeSH
- tubulin MeSH
The present experimental study was undertaken to provide information on nucleolar changes accompanying the apoptotic process in large or giant binucleate and multinucleate cells (LBMNCs). Such cells were present in a small but constant percentage in cultures of HL-60 cells. The apoptotic process was induced by photodynamic treatment (PDT) by means of 5-aminolaevulinic acid (ALA) as the precursor of the photosensitizer protoporphyrin IX and irradiation with broad spectrum blue light (BL). Nucleolar changes in LBMNCs were characterized by marked reduction or disappearance of silver stained particles representing AgNORs in nucleoli including the large ones. In addition, PDT also significantly reduced the number of nucleoli regardless of their size. These changes apparently reflected the decrease or cessation of nucleolar biosynthetic activities and resembled those which were previously observed in naturally maturing bone marrow megakaryocytes (Janoutová et al., 2001).
- MeSH
- apoptóza účinky léků MeSH
- barvení stříbrem MeSH
- buněčné jadérko chemie účinky léků ultrastruktura MeSH
- fotochemoterapie * MeSH
- fotosenzibilizující látky farmakologie MeSH
- granulocyty účinky léků patologie MeSH
- HL-60 buňky účinky léků patologie MeSH
- kyselina aminolevulová farmakologie MeSH
- leukemie farmakoterapie patologie MeSH
- lidé MeSH
- obrovské buňky účinky léků ultrastruktura MeSH
- organizátor jadérka chemie účinky léků ultrastruktura MeSH
- RNA analýza MeSH
- světlo MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fotosenzibilizující látky MeSH
- kyselina aminolevulová MeSH
- RNA MeSH
