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@inproceedings{842894,
author = {Slanina, Jiří and Adámková, Lenka and Koubíková, Ludmila and Hammerová, Jindřiška and Slaninová, Iva},
address = {Oxford, UK},
booktitle = {Book of Abstract of Conference of Functional Molecules from Natural Sources},
keywords = {Schisandra chinensis; dibenzocyclooctadiene lignans; multidrug resistance; MDR; MRP; cell cycle; cytotoxicity},
language = {eng},
location = {Oxford, UK},
publisher = {RSC Biotechnology Group},
title = {Deoxyschizandrin and gama-schizandrin restore the cytotoxic action of doxorubicin in multi-drug resistant lung cancer cells COR-L23/R},
year = {2009}
}
TY - JOUR
ID - 842894
AU - Slanina, Jiří - Adámková, Lenka - Koubíková, Ludmila - Hammerová, Jindřiška - Slaninová, Iva
PY - 2009
TI - Deoxyschizandrin and gama-schizandrin restore the cytotoxic action of doxorubicin in multi-drug resistant lung cancer cells COR-L23/R
PB - RSC Biotechnology Group
CY - Oxford, UK
KW - Schisandra chinensis
KW - dibenzocyclooctadiene lignans
KW - multidrug resistance
KW - MDR
KW - MRP
KW - cell cycle
KW - cytotoxicity
N2 - Schisandra chinensis (Schisandraceae) is a well-known medicinal plant in traditional Chinese medicine. The fruits and seeds have been used for centuries as a tonic and antitussive. Many studies have indicated that the active ingredients are lignans possessing an unusual structure derived from dibenzo[a,c]cyclooctadiene, which have been shown to possess a broad range of biological effects, including hepatoprotective and antiviral properties. Recently, dibenzocyclooctadiene lignans have been discussed as compounds that are able to overcome multidrug resistance. Nine dibenzo[a,c]cyclooctadiene lignans, schizandrin, gomisin A, gomisin N, gomisin J, angeloylgomisin H, tigloylgomisin P, deoxyschizandrin, gama-schizandrin and wuweizisu C, isolated from seeds of Schisandra chinensis, were examined for their effect on multidrug resistance, as well as their anti-proliferative activities. COR-L23/R, a multidrug-resistant sub-line over-expressing multidrug resistance-associated proteins 1 and 2 (MRP1 and MRP2) and its parent cell line COR-L23 (human lung cell carcinoma) were used. Our observations showed that COR-L23/R was nearly hundred times more resistant to doxorubicin than the parental line COR-L23; although both cell lines were similarly sensitive to lignans treatment, indicating that the lignans are not expelled from the resistant cells. We found that two lignans, R-(+)-deoxyschizandrin and R,S-( )-gama-schizandrin at relatively non-toxic concentrations restored the cytotoxic action of doxorubicin, a MRP1 substrate, to COR-L23/R cells. Moreover, R-(+)-deoxyschizandrin and R,S-( )-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 R-(+)-deoxyschizandrin and R,S-( )-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 -
SLANINA, Jiří, Lenka ADÁMKOVÁ, Ludmila KOUBÍKOVÁ, Jindřiška HAMMEROVÁ and Iva SLANINOVÁ. Deoxyschizandrin and gama-schizandrin restore the cytotoxic action of doxorubicin in multi-drug resistant lung cancer cells COR-L23/R. In \textit{Book of Abstract of Conference of Functional Molecules from Natural Sources}. Oxford, UK: RSC Biotechnology Group, 2009, 1 pp.
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