The Korean Journal of Physiology and Pharmacology

  • 제15권5호
  • /
  • Pages.279-283
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  • 2011
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  • 1226-4512(pISSN)
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  • 2093-3827(eISSN)
대한약리학회 (The Korean Society of Pharmacology)
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Quercetin-induced Growth Inhibition in Human Bladder Cancer Cells Is Associated with an Increase in $Ca^{2+}$-activated $K^+$ Channels

  • Kim, Yang-Mi (Department of Physiology, College of Medicine, Chungbuk National University) ;
  • Kim, Wun-Jae (Department of Urology, College of Medicine, Chungbuk National University) ;
  • Cha, Eun-Jong (Department of Biomedical Engineering, College of Medicine, Chungbuk National University)
  • 투고 : 2011.08.12
  • 심사 : 2011.10.09
  • 발행 : 2010.10.30
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초록

Quercetin (3,3',4',5,7-pentahydroxyflavone) is an attractive therapeutic flavonoid for cancer treatment because of its beneficial properties including apoptotic, antioxidant, and antiproliferative effects on cancer cells. However, the exact mechanism of action of quercetin on ion channel modulation is poorly understood in bladder cancer 253J cells. In this study, we demonstrated that large conductance $Ca^{2+}$-activated $K^+$ ($BK_{Ca}$) or MaxiK channels were functionally expressed in 253J cells, and quercetin increased $BK_{Ca}$ current in a concentration dependent and reversible manner using a whole cell patch configuration. The half maximal activation concentration ($IC_{50}$) of quercetin was $45.5{\pm}7.2{\mu}m$. The quercetin-evoked $BK_{Ca}$ current was inhibited by tetraethylammonium (TEA; 5 mM) a non-specific $BK_{Ca}$ blocker and iberiotoxin (IBX; 100 nM) a $BK_{Ca}$-specific blocker. Quercetin-induced membrane hyperpolarization was measured by fluorescence-activated cell sorting (FACS) with voltage sensitive dye, bis (1,3-dibutylbarbituric acid) trimethine oxonol ($DiBAC_4$2(3); 100 nM). Quercetin-evoked hyperpolarization was prevented by TEA. Quercetin produced an antiproliferative effect ($30.3{\pm}13.5%$) which was recovered to $53.3{\pm}10.5%$ and $72.9{\pm}3.7%$ by TEA and IBX, respectively. Taken together our results indicate that activation of $BK_{Ca}$ channels may be considered an important target related to the action of quercetin on human bladder cancer cells.

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