J 2009

Dibenzocyclooctadiene lignans overcome drug resistance in lung cancer cells - Study of structure-activity relationship

SLANINOVÁ, Iva, Lenka BŘEZINOVÁ, Ludmila KOUBÍKOVÁ and Jiří SLANINA

Basic information

Original name

Dibenzocyclooctadiene lignans overcome drug resistance in lung cancer cells - Study of structure-activity relationship

Authors

SLANINOVÁ, Iva (203 Czech Republic, guarantor), Lenka BŘEZINOVÁ (203 Czech Republic), Ludmila KOUBÍKOVÁ (203 Czech Republic) and Jiří SLANINA (203 Czech Republic)

Edition

Toxicology in Vitro, Elsevier, 2009, 0887-2333

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 2.060

RIV identification code

RIV/00216224:14110/09:00029837

Organization unit

Faculty of Medicine

UT WoS

000269551500013

Keywords in English

COR-L23/R; cytotoxicity; doxorubicin; dibenzocyclooctadiene lignans; multidrug resistance; MRP protein

Tags

International impact, Reviewed
Změněno: 8/1/2011 19:59, Mgr. Jiří Slanina, Ph.D.

Abstract

ORIG CZ

V originále

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.

In Czech

Panel devíti dibenzo [a, c] cyclooctadienových lignanů (schizandrin, gomisin, gomisin N, gomisin J, angeloylgomisin H, P tigloylgomisin, deoxyschizandrin, gama-schizandrin a wuweizisu C) byl studován z hlediska jako jejich anti-proliferační aktivity a jejich vlivu na mnohočetnou lékovou resistenci. COR-L23 / R, multidrug-rezistentní buněčná linie nadprodukující MRP1 protein, byla spolu mateřskou linií COR-L23 (lidský karcinom plic) použita pro pokusy. Zjistili jsme, že lignany deoxyschizandrin a gama-schizandrin v relativně netoxických koncentrací obnovují cytotoxické působení doxorubicinu na COR-L23 / R buňky. Deoxyschizandrin a gama-schizandrin vykazovaly také výrazně zvýšenou akumulaci doxorubicinu v rezistentních buňkách. Oba lignany samy neměly žádný vliv na buněčný cyklus, ale v kombinaci s sub-toxickou dávkou doxorubicinu zastavovaly buněčný vyklus v G2 / M fázi, což je účinek typický pro toxické dávky doxorubicinu. Naše výsledky naznačují, že deoxyschizandrin a gama-schizandrin mohou potencovat cytotoxický efekt doxorubicinu v doxorubicin resistentních buňkách COR-L23 / R a to zvýšením akumulace doxorubicinu uvnitř buněk. Společný strukturní znak aktivních, lignanů je R-biaryl konfigurace a absence hydroxy skupinou na C-8.

Links

GA522/07/0995, research and development project
Name: Regulace biosyntézy sekundarních metabolitů v buněčné kultuře Schisandra chinensis
Investor: Czech Science Foundation
LC06035, research and development project
Name: Centrum biofyzikální chemie, bioelektrochemie a bioanalýzy. Nové nástroje pro genomiku, proteomiku a biomedicínu.
Investor: Ministry of Education, Youth and Sports of the CR, Centre of Biophysical Chemistry, Bioelectrochemistry and Bioanalysis. New Tools for Genomics, Proteomics and Biomedicine
MSM0021622415, plan (intention)
Name: Molekulární podstata buněčných a tkáňových regulací
Investor: Ministry of Education, Youth and Sports of the CR, Molecular basis of cell and tissue regulations