Kim, Yong Kee Song, Yong Jin Seo, Dong-Wan Kang, Dong-Won Lee, Hoi Young Rhee, Dong-Kwon Han, Jeung-Whan Ahn, Chan Mug Lee, Seokjoon Kim, Su-Nam 2024-01-21T01:05:55Z 2024-01-21T01:05:55Z 2021-09-02 2007-03-30 0006-291X https://pubs.kist.re.kr/handle/201004/134518 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)betizamide (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. (c) 2007 Elsevier Inc. All rights reserved. English ACADEMIC PRESS INC ELSEVIER SCIENCE POTENT CYCLOPROPYLDIBENZOSUBERANE MODULATOR CANCER CHEMOPREVENTION TAXOL BINDS CURCUMIN LY335979 TRANSPORTERS MICROTUBULES MECHANISM THERAPY INVITRO Reversal of multidrug resistance by 4-chloro-N-(3-((E)-3-(4-hydroxy-3-methoxyphenyl)acryloyl)phenyl)benzamid e through the reversible inhibition of P-glycoprotein Article 10.1016/j.bbrc.2007.01.117 1 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.355, no.1, pp.136 - 142 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 355 1 136 142 scie scopus 000244641200023 2-s2.0-33847017659 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article POTENT CYCLOPROPYLDIBENZOSUBERANE MODULATOR CANCER CHEMOPREVENTION TAXOL BINDS CURCUMIN LY335979 TRANSPORTERS MICROTUBULES MECHANISM THERAPY INVITRO multidrug resistance P-glycoprotein curcumin 4-chloro-N-(3-((E)-3-(4-hydroxy-3-methoxyphenyl)acryloyl)phenyl)benzamid e