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Inhibition of P-glycoprotein by natural products in human breast cancer cells
- Title
- Inhibition of P-glycoprotein by natural products in human breast cancer cells
- Authors
- Soo Y.C.; Min K.S.; Na H.K.; Jung O.J.; Eun J.G.; Hwa J.L.
- Ewha Authors
- 이화정
- SCOPUS Author ID
- 이화정
- Issue Date
- 2005
- Journal Title
- Archives of Pharmacal Research
- ISSN
- 0253-6269
- Citation
- Archives of Pharmacal Research vol. 28, no. 7, pp. 823 - 828
- Indexed
- SCIE; SCOPUS; KCI
- Document Type
- Article
- Abstract
- Multidrug resistance (MDR) is one of the most significant obstacles in cancer chemotherapy. One of the mechanisms involved in the development of MDR is the over-expression of P-glycoprotein (P-gp). It is widely known that natural compounds found in vegetables, fruits, plantderived beverages and herbal dietary supplements not only have anticancer properties, but may also modulate P-gp activity. Therefore, the purpose of this investigation was to examine the effects of naturally occurring products on P-gp function in human breast cancer cell lines, MCF-7 (sensitive) and MCF-7/ADR (resistant). The accumulation of daunomycin (DNM), a Pgp substrate, was greater in the sensitive cells compared to the resistant cells, while the efflux of DNM was higher in the resistant cells compared to the sensitive cells over a period of 2 h. The IC50 value of DNM in the resistant cells was about 22 times higher than that in the sensitive cells, indicating an over-expression of P-gp in the resistant cells, MCF-7/ADR. All of the compounds tested, with the exception of fisetin, significantly decreased the IC50 value of DNM. Biochanin A showed the greatest increase in [3H]-DNM accumulation, increasing by 454.3 ± 19.5% in the resistant cells, whereas verapamil, the positive control, increased the accumulation by 229.4 ± 17.6%. Also, the accumulation of [3H]-DNM was increased substantially by quercetin and silymarin while it was reduced by fisetin. Moreover, biochanin A, silymarin, and naringenin significantly decreased DNM efflux from MCF-7/ADR cells compared with the control. These results suggest that some flavonoids such as biochanin A and silymarin may reverse MDR by inhibiting the P-gp function.
- DOI
- 10.1007/BF02977349
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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