The effect of lignans from schisandra chinensis on drug resistance of lung cancer cells
| Authors | |
|---|---|
| Year of publication | 2009 |
| Type | Article in Proceedings |
| Conference | XIII. Setkání biochemiků a molekulárních biologů |
| MU Faculty or unit | |
| Citation | |
| Field | Other medical specializations |
| Keywords | lignans; schizandrine; schisandra chinensis; cancer multidrug resistance; MDR; MRP |
| Description | Cancer multidrug resistance is one of the major causes of failure of chemotherapy. Overexpression of the ATP binding cassette members, particularly Pglycoprotein (Pgp, ABCB1) and family of multidrug resistance-associated proteins (MRP1 to MRP9) exporting drugs out of the cells, are responsible for most cases of clinical cancer multidrug resistance. Dibenzo[a,c]cyclooctadiene lignans are natural products originated from Schisandra chinensis (Schisandraceae), a well known medicinal plant in traditional Chinese medicine. These lignans 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. A panel of nine dibenzo[a,c]cyclooctadiene lignans (schizandrin, gomisin A, gomisin N, gomisin J, angeloylgomisin H, tigloylgomisin P, deoxyschizandrin, g-schizandrin and wuweizisu C), isolated from seeds of S. chinensis, was examined for their effect on multidrug resistance. COR-L23/R, a multidrug resistant sub line overexpressing multidrug resistance associated protein 1 (MRP1) together with its parent cell line CORL23 (human lung cell carcinoma) were used. We found that deoxyschizandrin and gamaschizandrin at relatively nontoxic concentrations restored the cytotoxic action of doxorubicin to CORL23/R cells. Moreover, deoxyschizandrin and gamaschizandrin showed the greatest ability to enhance the accumulation of doxorubicin in drug resistant cells. Lignans alone had no effect on the cell cycle, however, in combination with subtoxic doses of doxorubicin, cell were arrested in the G2/M phase, which is typical for doxorubicin at toxic doses. Our results suggest that deoxyschizandrin and gamaschizandrin potentiate the effect of doxorubicin in doxorubicin resistant lung cancer cells by increasing the accumulation of doxorubicin inside the cells. This work was supported by the Czech Science Foundation (project No. 522/07/0995) and the Ministry of Education of the Czech Republic (VZ MSM0021622415 and LC06077). |
| Related projects: |