Please use this identifier to cite or link to this item: http://cmuir.cmu.ac.th/jspui/handle/6653943832/38520
Title: Biochemical mechanism of modulation of human p-glycoprotein by stemofoline
Authors: Chanmahasathien,W.
Ohnuma,S.
Ambudkar,S.V.
Limtrakul,P.N.
Keywords: Analytical Chemistry
Drug Discovery
Pharmaceutical Science
Molecular Medicine
Pharmacology
Organic Chemistry
Complementary and Alternative Medicine
Issue Date: 25-Jul-2011
Publisher: Georg Thieme Verlag
Abstract: The resistance to chemotherapeutic drugs by cancer cells is considered to be one of the major obstacles for success in the treatment of cancer. A major mechanism underlying this multidrug resistance is the overexpression of P-glycoprotein (P-gp), resulting in insufficient drug delivery to the tumor sites. A previous study has shown that stemofoline, an alkaloid isolated from Stemona burkillii, could enhance the sensitivity of chemotherapeutics in a synergistic fashion. In the present study, we have focused on the effect of stemofoline on the modulation of P-gp function in a multidrug resistant human cervical carcinoma cell line (KB-V1). The effects of stemofoline on a radiolabeled drug, [ 3H]-vinblastine, and fluorescent P-gp substrates, rhodamine 123 and calcein-AM accumulation or retention were investigated to confirm this finding. Stemofoline could increase the accumulation or retention of radiolabeled drugs or fluorescent P-gp substrates in a dose-dependent manner. For additional studies on drug-P-gp binding, P-gp ATPase activity was stimulated by stemofoline in a concentration-dependent manner. More evidence was offered that stemofoline inhibits the effect on photoaffinity labeling of P-gp with [ 125I]-iodoarylazidoprazosin in a concentration-dependent manner. These data indicate that stemofoline may interact directly with P-gp and inhibit P-gp activity, whereas stemofoline has no effect on P-gp expression. Taken together, the results exhibit that stemofoline possesses an effective MDR modulator, and may be used in combination with conventional chemotherapeutic drugs to reverse MDR in cancer cells. © Georg Thieme Verlag KG Stuttgart · New York.
URI: http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84155172846&origin=inward
http://cmuir.cmu.ac.th/handle/6653943832/38520
ISSN: 00320943
Appears in Collections:PHARMACY: Journal Articles

Files in This Item:
There are no files associated with this item.


Items in CMUIR are protected by copyright, with all rights reserved, unless otherwise indicated.