RLIP76 (RALBP1)-mediated transport of leukotriene C4 (LTC4) in cancer cells: implications in drug resistance

International Journal of Cancer. Journal International Du Cancer
Rajendra SharmaSanjay Awasthi

Abstract

Increased active transport of LTC(4) observed frequently in multidrug-resistant cancer cells have been attributed to ABC-transporter proteins particularly, MRP1. We have demonstrated recently that a novel non-ABC transporter, RLIP76 (RALBP1) can also mediate ATP-dependent transport of GSH-conjugates (GS-E) as well as doxorubicin (DOX). We demonstrate RLIP76 reconstituted in artificial liposomes can catalyze ATP-dependent transport of LTC(4), which can be modulated by PKC-alpha. The ATPase activity of E. coli expressed homogenous RLIP76 was stimulated in a saturable fashion by LTC(4) with half maximal stimulation at 130 nM. Proteoliposomes reconstituted with RLIP76 catalyzed temperature and osmolar sensitive ATP-dependent transport of LTC(4) with K(m) values of 5.1 mM and 210 nM for ATP and LTC(4), respectively. V(max) for transport was found to be 3.2 nmol/min/mg. Colchicine inhibited LTC(4) transport to 50% at 5.8 microM. PKC-alpha catalyzed phosphorylation of RLIP76 and increased its transport activity by 2-3-fold. Membrane vesicles prepared from the small (SCLC) and non-small (NSCLC) lung cancer cell lines as well as HL-60 (leukemia) and U937 (lymphoma) cell lines exhibited ATP-dependent transport of LTC(4), which was inhibi...Continue Reading

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Citations

Jan 30, 2007·Cancer Metastasis Reviews·Sushma YadavSanjay Awasthi
Feb 20, 2013·Biochemical Pharmacology·Archana SehrawatSanjay Awasthi
May 14, 2008·The Journal of Biological Chemistry·Sharad S SinghalSanjay Awasthi
Feb 26, 2010·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Yogesh C AwasthiRajendra Sharma
Sep 8, 2010·American Journal of Physiology. Lung Cellular and Molecular Physiology·Y Michael ShimRobert M Strieter
Jul 17, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sanjay AwasthiArthur E Frankel
Sep 29, 2005·BMC Neuroscience·Sanjay AwasthiDamir Janigro
Apr 4, 2006·FEBS Letters·Sharad S SinghalSanjay Awasthi
Oct 4, 2006·Expert Opinion on Drug Metabolism & Toxicology·Aalok NadkarSanjay Awasthi
Aug 8, 2006·Biochemical and Biophysical Research Communications·Sharad S SinghalSanjay Awasthi
Jun 14, 2005·Biochemical Pharmacology·Sharad S SinghalSanjay Awasthi
May 30, 2015·Pharmaceutical Research·Sharad S SinghalSanjay Awasthi
Sep 16, 2008·FEBS Letters·Sharad S SinghalSanjay Awasthi
Apr 20, 2019·Journal of Ovarian Research·Dody Houston Billhaq, Seunghyung Lee
Mar 25, 2018·Proceedings of the National Academy of Sciences of the United States of America·Sanjay AwasthiSharad S Singhal
Feb 21, 2006·Cancer Research·Sharad S SinghalSanjay Awasthi
Jul 19, 2005·Cancer Research·Sanjay AwasthiYogesh C Awasthi
Nov 6, 2008·Biochemical Pharmacology·Sharad S SinghalJyotsana Singhal
Jan 26, 2010·Biochemical Pharmacology·Rit VatsyayanSharad S Singhal

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