PÁCHNIKOVÁ, Gabriela, Ludmila KOUBÍKOVÁ, Jiří SLANINA, Martina ČARNECKÁ a Iva SLANINOVÁ. Effect of dibenzocyclooctadiene lignans on multidrug resistant promyelotic leukaemia cells. In Natural Anticancer Drugs, 30.6.-4.7.2012, Olomouc. 2012. ISSN 1213-8118.
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Základní údaje
Originální název Effect of dibenzocyclooctadiene lignans on multidrug resistant promyelotic leukaemia cells
Autoři PÁCHNIKOVÁ, Gabriela (703 Slovensko, garant, domácí), Ludmila KOUBÍKOVÁ (203 Česká republika, domácí), Jiří SLANINA (203 Česká republika, domácí), Martina ČARNECKÁ (703 Slovensko, domácí) a Iva SLANINOVÁ (203 Česká republika, domácí).
Vydání Natural Anticancer Drugs, 30.6.-4.7.2012, Olomouc, 2012.
Další údaje
Originální jazyk angličtina
Typ výsledku Konferenční abstrakt
Obor 30000 3. Medical and Health Sciences
Stát vydavatele Česká republika
Utajení není předmětem státního či obchodního tajemství
WWW URL
Impakt faktor Impact factor: 0.990
Kód RIV RIV/00216224:14110/12:00057524
Organizační jednotka Lékařská fakulta
ISSN 1213-8118
Klíčová slova anglicky dibenzocyclooctadiene; promyelotic leukaemia cells; cancer
Příznaky Mezinárodní význam
Změnil Změnil: Mgr. Michal Petr, učo 65024. Změněno: 3. 9. 2012 11:07.
Anotace
In this study we used multidrug resistant promyelotic leukaemia cells overexpressing MDR1 (P-glycoprotein), the most common member of ABC transporters family (HL60/ MDR). The ability to overcome multidrug resistance was examined in the panel of dibenzo[a,c]cyclooctadiene lignans, schizandrin, gomisin A, gomisin N, angeloylgomisin H, tigloylgomisin P, deoxyschizandrin-dicarbaldehyde, wuweizisu C, and S(-)- and R(+)-enantiomers of deoxyschizandrin, y-schizandrin and gomisin J. The lignans were isolated from Schisandra chinensis seeds or prepared semisynthetically. We observed that resistant HL60/MDR was nearly hundred times more resistant to doxorubicin than the parental line HL60; although both cell lines were similarly sensitive to lignans treatment, indicating that the lignans are not exported from the resistant cells. Using doxorubicin accumulation assay we demonstrated that all lignans significantly enhanced the accumulation of doxorubicin in drug resistant cells. The results were comparable or even higher than Verapamil used as a positive control. Comparing enantiomers of individual lignans, we observed higher effect of R(+)-y-schizandrin. On WST and PI- exclusion assay we demonstrated that the lignans enhanced cytotoxic effect of sub-toxic concentrations of doxorubicin. Deoxyschizandrin and Gomisin N were selected for further studies because of high activity in accumulation assay. Deoxyschizandrin and gomisin N 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, what is typical for toxic doses of doxorubicin. The results proved the ability of DBL to overcome MDR resistance in P-glycoprotein overexpressing HL60 cell, due to the increasing doxorubicin accumulation inside the cells. DBL represents substances promising for treatment of multidrug resistant cancer.
Návaznosti
GA522/07/0995, projekt VaVNázev: Regulace biosyntézy sekundarních metabolitů v buněčné kultuře Schisandra chinensis
Investor: Grantová agentura ČR, Standardní projekty
VytisknoutZobrazeno: 29. 11. 2021 13:52