Volume 22, Issue 2, 15 February 2015, Pages 301–307
Natural lignans from Arctium lappa modulate P-glycoprotein efflux function in multidrug resistant cancer cells
Abstract
Arctium lappa
is a well-known traditional medicinal plant in China (TCM) and Europe
that has been used for thousands of years to treat arthritis, baldness
or cancer. The plant produces lignans as secondary metabolites which
have a wide range of bioactivities. Yet, their ability to reverse
multidrug resistance (MDR) in cancer cells has not been explored. In
this study, we isolated six lignans from A. lappa seeds, namely
arctigenin, matairesinol, arctiin, (iso)lappaol A, lappaol C, and
lappaol F. The MDR reversal potential of the isolated lignans and the
underlying mechanism of action were studied using two MDR cancer cell
lines, CaCo2 and CEM/ADR 5000 which overexpress P-gp and other ABC
transporters. In two-drug combinations of lignans with the cytotoxic
doxorubicin, all lignans exhibited synergistic effects in CaCo2 cells
and matairesinol, arctiin, lappaol C and lappaol F display synergistic
activity in CEM/ADR 5000 cells. Additionally, in three-drug combinations
of lignans with the saponin digitonin and doxorubicin MDR reversal
activity was even stronger enhanced. The lignans can increase the
retention of the P-gp substrate rhodamine 123 in CEM/ADR 5000 cells,
indicating that lignans can inhibit the activity of P-gp. Our study
provides a first insight into the potential chemosensitizing activity of
a series of natural lignans, which might be candidates for developing
novel adjuvant anticancer agents.
Graphical Abstract
Keywords
- Arctium lappa;
- Lignans;
- Multidrug resistance;
- P-glycoprotein;
- Cancer cells
- Corresponding author. Tel.:
+49 (0) 6221 544881; fax: +49 (0) 6221 544884.
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