Journal of Pharmaceutical Investigation

  • 제33권4호
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  • Pages.305-310
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  • 2003
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  • 2093-5552(pISSN)
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  • 2093-6214(eISSN)
한국약제학회 (The Korean Society of Pharmaceutical Sciences and Technology)
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인체 자궁암 세포에서 플라보노이드에 의한 P-당단백질의 활성 조절

Modulation of P-glycoprotein Activity by Flavonoids in Human Uterine Sarcoma Cells

  • 고은정 (이화여자대학교 약학대학) ;
  • 정수연 (이화여자대학교 약학대학) ;
  • 김나형 (이화여자대학교 약학대학) ;
  • 이화정 (이화여자대학교 약학대학)
  • 발행 : 2003.12.20
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초록

One of the possible mechanisms of multi-drug resistance found in cancer cells is the over-expression of P­glycoprotein (P-gp). Studies have shown that compounds in plants including vegetables and fruits not only have anticancer activities but may also modulate P-gp activity. The effect of flavonoids and organic isothiocyanate on P-gp activity was studied in human uterine sarcoma cell lines, MES-SA (sensitive) and MES-SA/DX5 (resistant) cells. The accumulation of daunomycin (DNM), a P-gp substrate, was approximately 10 times greater in the sensitive cell as compared to the resistant cells over the entire time course (up to 2 hours). The positive control, verapamil increased the two hour accumulation of DNM while quercetin decreased that of DNM in the resistant cells. 1-Naphtyl-isothiocyanate (NITC) showed no effect on the two hour accumulation of DNM. The $IC_{50}$ values for DNM in the resistant cells was about 20 times higher than that observed in the sensitive cells $(10.1{\pm}1.7\;{\mu}M\;vs.\;0.58{\pm}0.28\;{\mu}M)$. Verapamil reduced the $IC_{50}$ value for DNM whereas flavonoids (quercetin and fisetin) increased those for DNM in the resistant cells.

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