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@article{869289,
author = {Slaninová, Iva and Březinová, Lenka and Koubíková, Ludmila and Slanina, Jiří},
article_number = {6},
keywords = {COR-L23/R; cytotoxicity; doxorubicin; dibenzocyclooctadiene lignans; multidrug resistance; MRP protein},
language = {eng},
issn = {0887-2333},
journal = {Toxicology in Vitro},
title = {Dibenzocyclooctadiene lignans overcome drug resistance in lung cancer cells - Study of structure-activity relationship},
url = {http://www.sciencedirect.com/},
volume = {23},
year = {2009}
}
TY - JOUR
ID - 869289
AU - Slaninová, Iva - Březinová, Lenka - Koubíková, Ludmila - Slanina, Jiří
PY - 2009
TI - Dibenzocyclooctadiene lignans overcome drug resistance in lung cancer cells - Study of structure-activity relationship
JF - Toxicology in Vitro
VL - 23
IS - 6
SP - 1047-1054
EP - 1047-1054
PB - Elsevier
SN - 08872333
KW - COR-L23/R
KW - cytotoxicity
KW - doxorubicin
KW - dibenzocyclooctadiene lignans
KW - multidrug resistance
KW - MRP protein
UR - http://www.sciencedirect.com/
N2 - A panel of nine dibenzo[a,c]cyclooctadiene lignans, schizandrin, gomisin A, gomisin N, gomisin J, angeloylgomisin H, tigloylgomisin P, deoxyschizandrin, gama-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 gama-schizandrin at relatively non-toxic concentrations restored the cytotoxic action of doxorubicin to COR-L23/R cells. Deoxyschizandrin and gama-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 gama-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.
ER -
SLANINOVÁ, Iva, Lenka BŘEZINOVÁ, Ludmila KOUBÍKOVÁ a Jiří SLANINA. Dibenzocyclooctadiene lignans overcome drug resistance in lung cancer cells - Study of structure-activity relationship. \textit{Toxicology in Vitro}. Elsevier, 2009, roč.~23, č.~6, s.~1047-1054. ISSN~0887-2333.
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