Abstract
Multidrug resistance (MDR) mediated by the overexpression of the drug efflux protein P-glycoprotein is one of the major obstacles to successful cancer chemotherapy. The development of safe and effective MDR-reversing agents is an important approach to addressing this problem clinically. In this study, we evaluated the P-gp-modulatory potential of O-(4-ethoxyl-butyl)-berbamine (EBB), a novel calmodulin antagonist and derivative of bisbenzylisoquinoline alkaloid, which significantly improved the chemosensitivity of P-glycoprotein-mediated multidrug-resistant cells to doxorubicin compared with the efficacy of a conventional P-glycoprotein inhibitor, verapamil. EBB not only blocked the function of P-glycoprotein confirmed by the fact that EBB increased intracellular accumulation of rhodamine 123 and doxorubicin but also inhibited the expression of P-glycoprotein actualized by downregulating P-glycoprotein. Furthermore, our results showed that cotreatment with EBB and doxorubicin resulted in marked G(2)/M arrest and apoptosis of MCF-7/ADR cells, accompanied by down-regulation of the proteins cdc2/p34 and cyclin B1 and increased the levels of calcium ions. Taken together, these results suggest that cotreatment with EBB and doxorubici...Continue Reading
References
Jul 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·E B Mechetner, I B Roninson
Jan 1, 1992·Cytometry·M BriffodJ Rouëssé
Oct 15, 1986·Biochemical and Biophysical Research Communications·Y H Xu, S P Zhang
Jan 4, 1980·Science·W Y Cheung
Dec 16, 1994·Science·L H Hartwell, M B Kastan
Mar 24, 2000·European Journal of Pharmacology·C Marbeuf-GueyeA Garnier-Suillerot
Nov 9, 2000·European Journal of Pharmacology·F UshigomeY Sawada
Dec 21, 2000·The Journal of Biological Chemistry·S Y ShinY H Lee
May 2, 2001·Biochemical Pharmacology·L J GreenC A Slapak
Oct 5, 2001·Molecular and Cellular Biology·P VillalongaN Agell
Mar 21, 2002·Nature Reviews. Cancer·Michael M GottesmanSusan E Bates
Mar 28, 2002·Cellular and Molecular Life Sciences : CMLS·A Di PietroD Barron
Apr 5, 2003·Science·Nicolas Demaurex, Clark Distelhorst
Nov 18, 2003·International Journal of Cancer. Journal International Du Cancer·Ken ShiozawaShigeru Kohno
Dec 13, 2003·Endocrine Reviews·Christina R Kahl, Anthony R Means
Dec 23, 2003·Life Sciences·Elod Kortvely, Karoly Gulya
Aug 16, 2005·Biochemical and Biophysical Research Communications·Zdena SulováAlbert Breier
Jan 6, 2006·Biological & Pharmaceutical Bulletin·Shuji Kitagawa
Feb 7, 2006·Cancer Letters·Guanghui WangXinsheng Yao
Mar 18, 2006·Leukemia Research·Hanan GalskiArnon Nagler
Jul 18, 2006·Current Drug Targets·E TeodoriF Gualtieri
Aug 29, 2006·Biochemical and Biophysical Research Communications·Jing QiDongsheng Xiong
Citations
Feb 21, 2013·Chemical Biology & Drug Design·Chao MaZhiwei Cao
Mar 13, 2014·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Xiaoli Jin, Yulian Wu
Nov 6, 2013·Biochimica Et Biophysica Acta·Martin W Berchtold, Antonio Villalobo
Sep 6, 2012·Journal of Zhejiang University. Science. B·Shailendra Kapoor
Apr 14, 2015·BioMed Research International·Paul J DavisShaker A Mousa
Oct 18, 2012·Blood·Ying GuRongzhen Xu
May 17, 2012·Journal of Asian Natural Products Research·Ping HeFeng-Peng Wang
Oct 27, 2016·Oncotarget·Ting LiuWenhua Li
Aug 11, 2020·The Journal of International Medical Research·Yachun LiWanzhong Yin
Jan 8, 2014·Oncology Letters·Liang XuShutong Zhang
Feb 9, 2017·The Journal of Biological Chemistry·Zhigang LiDavid B Sacks
Sep 9, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Feng JiaLinshan Fu
Apr 14, 2017·Molecular and Cellular Biochemistry·Huihan WangZhuogang Liu
Jul 27, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Lili LiuYing Cao