Inhibition of P-glycoprotein by natural products in human breast cancer cells

Yeon Chung Soo, Kyung Sung Min, Hyung Kim Na, Ok Jang Jung, Jung Go Eun, Jeong Lee Hwa

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106 Scopus citations


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.

Original languageEnglish
Pages (from-to)823-828
Number of pages6
JournalArchives of Pharmacal Research
Issue number7
StatePublished - 31 Jul 2005

Bibliographical note

Funding Information:
This work was supported by the Korea Science and Engineering Foundation for the National R&D Program for Enhancing R&D Infrastructure of Women's University \[R06-2002-011-01002-0(2002)\]. Soo Yeon Chung was supported by a Scholarship from the Health Fellowship Foundation of YuHan Corp.


  • Daunomycin
  • MCF-7/ADR Cells
  • Natural Products
  • P-glycoprotein


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