2005
Microtubules as targets of alkaloids in cancer treatment
SLANINOVÁ, Iva a Zdenka SLUNSKÁZákladní údaje
Originální název
Microtubules as targets of alkaloids in cancer treatment
Název česky
Mikrotubuly jako terče alkaloidů v terapii nádorů
Autoři
SLANINOVÁ, Iva a Zdenka SLUNSKÁ
Vydání
Praha, Sborník XIII. Cytoskeletálního klubu, od s. 25-25, 1 s. 2005
Nakladatel
Československá biologická společnost
Další údaje
Jazyk
angličtina
Typ výsledku
Stať ve sborníku
Obor
30200 3.2 Clinical medicine
Stát vydavatele
Česká republika
Utajení
není předmětem státního či obchodního tajemství
Organizační jednotka
Lékařská fakulta
Klíčová slova anglicky
benzophenanthridine alkaloids; cancer; cytostatics; anti-mitotic drugs; microtubules
Změněno: 2. 6. 2005 14:49, RNDr. JUDr. Vladimír Šmíd, CSc.
V originále
A large number of chemical compounds, many of which are derived from natural products, bind to tubulin and inhibit cell proliferation at the metaphase/anaphase transition of mitosis by acting on the mitotic spindle. In our contribution, we briefly summarize the current understanding of interactions of microtubules with alkaloids using as anti-tumor agents, i.e. Vinca alkaloides, taxanes, colchicine and others. Microtubule-interacting drugs are important agents in cancer chemotherapy. Not only the presence of MT, but also theirs dynamics are important for cell processes dependent on MT (intracellular transport, motility, morphogenesis, mitosis). Dynamic properties of MTs include dynamic instability and treadmilling. Disruption of tubulin-MT equlibrium and/or MT stabilization can lead to the same consequences as microtubule disruption. Two classes of anti-tumor drugs was found to inhibit cell division by acting on microtubules: 1) taxanes that block MT depolymerization and stabilize MT; 2) vinca alkaloids and colchicine that inhibit MT polymerization. Three types of toxins according to binding site on b-tubulin are recognized to date: 1) colchicine site (close to a/b interface); 2) vinca alkaloids area; 3) taxane binding pocket. Several new compounds with anti-mitotic properties are effective chemoterapeutic agents and thus the search for new tubulin-binding drugs is important for the cancer therapy. Recently we study antiproliferative properties of benzo[c]phenanthridine alkaloids. Anti-microtubular effect is one of the discussed mechanism of these alkaloids action. Wolf and Knippling (1993) described that benzo[c]phenanthridine derivatives chelidonine, sanguinarine and chelerythrine inhibit taxol-mediated polymerisation of rat brain tubulin in vitro and that sanguinarine and chelerythrine affect colchicine and podophyllotoxine binding on MT. We described the effect of sanguinarine, chelerythrine, sanguilutine, chelilutine (Slaninová et al., 2001) and recently also other derivatives sanguirubine and chelirubine on microtubules of HeLa cells. In cells cultivated with these alkaloids the microtubular network thining out from the cell periphery and at higher alkaloid concentrations MTs completely disappear. References: Slaninová, I., Táborská, E., Bochořáková, H., Slanina, J. Cell Biology and Toxicology: 17: 51-63. 2001. Wolf J, Knipling L. Biochemistry.32: 13334-13339.1993 Reviews for further reading: Checchi, P.M. et al., Ttrends in Pharmacol Sci:24. 361-365. 2003. Hadfield, J.A et al., Progress in Cell Cycle Research:5, 309-325. 2003. Wood, K.W. et al., Current Opin in Pharmacol.:1. 370-377.2001. Jordan, A.M. et al. Current Opin in Cell Biol. 10: 123-130. 1998. Sorger, P.K. et al. Current Opin in Cell Biol. 9: 807-814.1997. This work was supported by grants from Grant Agency of the Czech Republic (No. 525/04/0017 and 301/03/H005).
Česky
Existuje spousta látek přírodního původu, které se váži na mikrotubuly a způsobují zástavu proliferace v mitóze. Příspěvek shrnuje současné poznatky o interakcích mikrotubulů s alkaloidy a jejich význam v protinádorové terapii.
Návaznosti
| GA525/04/0017, projekt VaV |
| ||
| GD301/03/H005, projekt VaV |
|