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Reversal of multidrug resistance by 4-chloro-N-(3-((E)-3-(4-hydroxy-3-methoxyphenyl)acryloyl)phenyl)benzamide through the reversible inhibition of P-glycoprotein.
Biochem Biophys Res Commun. 2007 Mar 30; 355(1):136-42.BB

Abstract

Overexpression of P-glycoprotein (P-gp) is one of the major obstacles to successful cancer chemotherapy. In this study, we examined the ability of 4-chloro-N-(3-((E)-3-(4-hydroxy-3-methoxyphenyl)acryloyl)phenyl)benzamide (C-4) to reverse multidrug resistance (MDR) in P-gp expressing KBV20C cells. Treatment of KBV20C cells with C-4 led to a dramatic increase in paclitaxel- or vincristine-induced cytotoxicity without any cytotoxicity by itself. In parallel, C-4 treatment caused an increase in apoptotic cell death by paclitaxel or vincristine. Furthermore, C-4 treatment significantly increases in intracellular accumulation of fluorescent P-gp substrate rhodamine 123, indicating that C-4 treatment leads to reversal of the MDR phenotype resulting from an increased accumulation of anticancer drugs by inhibiting drug efflux function of P-gp. This notion is further supported by the observation that C-4 treatment potentiates paclitaxel-induced G(2)/M arrest of the cell cycle. In addition, the drug efflux function of P-gp was reversibly inhibited by C-4 treatment, while the expression level of P-gp was not affected. Collectively, our results describe the potential of C-4 to reverse the P-gp-mediated MDR phenotype through reversible inhibition of P-gp function, which may make it an attractive new agent for the chemosensitization of cancer cells.

Authors+Show Affiliations

College of Medicine, Kwandong University, Gangneung 210-701, Republic of Korea. yksnbk@kwandong.ac.krNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17286965

Citation

Kim, Yong Kee, et al. "Reversal of Multidrug Resistance By 4-chloro-N-(3-((E)-3-(4-hydroxy-3-methoxyphenyl)acryloyl)phenyl)benzamide Through the Reversible Inhibition of P-glycoprotein." Biochemical and Biophysical Research Communications, vol. 355, no. 1, 2007, pp. 136-42.
Kim YK, Song YJ, Seo DW, et al. Reversal of multidrug resistance by 4-chloro-N-(3-((E)-3-(4-hydroxy-3-methoxyphenyl)acryloyl)phenyl)benzamide through the reversible inhibition of P-glycoprotein. Biochem Biophys Res Commun. 2007;355(1):136-42.
Kim, Y. K., Song, Y. J., Seo, D. W., Kang, D. W., Lee, H. Y., Rhee, D. K., Han, J. W., Ahn, C. M., Lee, S., & Kim, S. N. (2007). Reversal of multidrug resistance by 4-chloro-N-(3-((E)-3-(4-hydroxy-3-methoxyphenyl)acryloyl)phenyl)benzamide through the reversible inhibition of P-glycoprotein. Biochemical and Biophysical Research Communications, 355(1), 136-42.
Kim YK, et al. Reversal of Multidrug Resistance By 4-chloro-N-(3-((E)-3-(4-hydroxy-3-methoxyphenyl)acryloyl)phenyl)benzamide Through the Reversible Inhibition of P-glycoprotein. Biochem Biophys Res Commun. 2007 Mar 30;355(1):136-42. PubMed PMID: 17286965.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reversal of multidrug resistance by 4-chloro-N-(3-((E)-3-(4-hydroxy-3-methoxyphenyl)acryloyl)phenyl)benzamide through the reversible inhibition of P-glycoprotein. AU - Kim,Yong Kee, AU - Song,Yong Jin, AU - Seo,Dong-Wan, AU - Kang,Dong-Won, AU - Lee,Hoi Young, AU - Rhee,Dong-Kwon, AU - Han,Jeung-Whan, AU - Ahn,Chan Mug, AU - Lee,Seokjoon, AU - Kim,Su-Nam, Y1 - 2007/01/30/ PY - 2007/01/20/received PY - 2007/01/23/accepted PY - 2007/2/9/pubmed PY - 2007/4/11/medline PY - 2007/2/9/entrez SP - 136 EP - 42 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 355 IS - 1 N2 - Overexpression of P-glycoprotein (P-gp) is one of the major obstacles to successful cancer chemotherapy. In this study, we examined the ability of 4-chloro-N-(3-((E)-3-(4-hydroxy-3-methoxyphenyl)acryloyl)phenyl)benzamide (C-4) to reverse multidrug resistance (MDR) in P-gp expressing KBV20C cells. Treatment of KBV20C cells with C-4 led to a dramatic increase in paclitaxel- or vincristine-induced cytotoxicity without any cytotoxicity by itself. In parallel, C-4 treatment caused an increase in apoptotic cell death by paclitaxel or vincristine. Furthermore, C-4 treatment significantly increases in intracellular accumulation of fluorescent P-gp substrate rhodamine 123, indicating that C-4 treatment leads to reversal of the MDR phenotype resulting from an increased accumulation of anticancer drugs by inhibiting drug efflux function of P-gp. This notion is further supported by the observation that C-4 treatment potentiates paclitaxel-induced G(2)/M arrest of the cell cycle. In addition, the drug efflux function of P-gp was reversibly inhibited by C-4 treatment, while the expression level of P-gp was not affected. Collectively, our results describe the potential of C-4 to reverse the P-gp-mediated MDR phenotype through reversible inhibition of P-gp function, which may make it an attractive new agent for the chemosensitization of cancer cells. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/17286965/Reversal_of_multidrug_resistance_by_4_chloro_N__3___E__3__4_hydroxy_3_methoxyphenyl_acryloyl_phenyl_benzamide_through_the_reversible_inhibition_of_P_glycoprotein_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(07)00175-1 DB - PRIME DP - Unbound Medicine ER -