A panel of nine dibenzo[a,c]cyclooctadiene lignans, schizandrin, gomisin A, gomisin N, gomisin J, angeloylgomisin H, tigloylgomisin P, deoxyschizandrin, gamma-schizandrin and wuweizisu C was examined for their effect on multidrug resistance, as well as their anti-proliferative activities. COR-L23/R, a multidrug resistant sub-line, which has been reported to over-express multidrug resistance-associated protein (MRP1), was used for the experiments together with its parent cell line COR-L23 (human lung cell carcinoma). We found that lignans deoxyschizandrin and gamma-schizandrin at relatively non-toxic concentrations restored the cytotoxic action of doxorubicin to COR-L23/R cells. Deoxyschizandrin and gamma-schizandrin also significantly enhanced the accumulation of doxorubicin in drug resistant cells. Both lignans alone had no effect on the cell cycle; however, when combined with sub-toxic doses of doxorubicin, they induced cell cycle arrest in the G2/M phase, which is typical for toxic doses of doxorubicin. Our results suggest that deoxyschizandrin and gamma-schizandrin potentiate the cytotoxic effect of doxorubicin in doxorubicin resistant lung cancer cells COR-L23/R by increasing the accumulation of doxorubicin inside the cells. The common structural feature of both active lignans is the R-biaryl configuration and the absence of a hydroxy group at C-8. Unlike the reversal effect, the cytotoxicity of lignans with the R-biaryl configuration was similar to that observed for lignans with the S-biaryl configuration.
- MeSH
- antibiotika antitumorózní aplikace a dávkování farmakologie metabolismus MeSH
- buněčné dělení účinky léků MeSH
- chemorezistence účinky léků MeSH
- cyklooktany aplikace a dávkování farmakologie chemie MeSH
- daunomycin aplikace a dávkování farmakologie metabolismus MeSH
- G2 fáze účinky léků MeSH
- lidé MeSH
- lignany aplikace a dávkování farmakologie chemie MeSH
- mnohočetná léková rezistence účinky léků MeSH
- nádorové buněčné linie MeSH
- nádory plic farmakoterapie metabolismus MeSH
- velkobuněčný karcinom farmakoterapie metabolismus MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH