| Functional characterization and molecular expression of large neutral amino acid transporter (LAT1) in human prostate cancer cells. | |
| | |
MedLine Citation:
|
PMID: 23270998 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
The primary objective of this study is to functionally characterize and provide molecular evidence of large neutral amino acid transporter (LAT1) in human derived prostate cancer cells (PC-3). We carried out the uptake of [3H]-tyrosine to assess the functional activity of LAT1. Reverse transcription-polymerase chain reaction (RT-PCR) analysis is carried out to confirm the molecular expression of LAT1. [3H]-tyrosine uptake is found to be time dependent and linear up to 60min. The uptake process does not exhibit any dependence on sodium ions, pH and energy. However, it is temperature dependent and found maximal at physiological temperature. The uptake of [3H]-tyrosine demonstrates saturable kinetics with K(m) and V(max) values of 34±3μM and 0.70±0.02 nanomoles/min/mg protein, respectively. It is strongly inhibited by large neutral (phenylalanine, tryptophan, leucine, isoleucine) and small neutral (alanine, serine, cysteine) but not by basic (lysine and arginine) and acidic (aspartic and glutamic acid) amino acids. Isoleucine-quinidine (Ile-quinidine) prodrug generates a significant inhibitory effect on [3H]-tyrosine uptake suggesting that it is recognized by LAT1. RT-PCR analysis provided a product band at 658 and 840bp, specific to LAT1 and LAT2, respectively. For the first time, this study demonstrates that LAT1, primarily responsible for the uptake of large neutral amino acids, is functionally active in PC-3 cells. Significant increase in the uptake generated by Ile-quinidine relative to quinidine suggests that LAT1 can be utilized for enhancing the cellular permeation of poor cell permeable anticancer drugs. Furthermore, this cell line can be utilized as an excellent in vitro model for studying the interaction of large neutral amino acid conjugated drugs with LAT1 transporter. |
| | |
Authors:
|
Mitesh Patel; Pranjali Dalvi; Mitan Gokulgandhi; Susamita Kesh; Tanvi Kohli; Dhananjay Pal; Ashim K Mitra |
Related Documents
:
|
21152098 - Identification of retinoic acid in a high content screen for agents that overcome the a... 6271418 - Angiotensin i recovery from plasma incubated with organic reagents. 1220558 - Correlation of serum aspirin esterase activity and half-life of salicylic acid. 21062318 - Involvement of extracellular oxidative burst in salicylic acid-induced stomatal closure... 9140558 - In vitro effects of an acidic by-product feed on bovine teeth. 16233168 - Characterization of factors that transform linoleic acid into di- and trihydroxyoctadec... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-12-24 |
Journal Detail:
|
Title: International journal of pharmaceutics Volume: - ISSN: 1873-3476 ISO Abbreviation: Int J Pharm Publication Date: 2012 Dec |
Date Detail:
|
Created Date: 2012-12-28 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 7804127 Medline TA: Int J Pharm Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2012. Published by Elsevier B.V. |
Affiliation:
|
Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO 64108, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Mucosa-plate for direct evaluation of mucoadhesion of drug carriers.
Next Document: Antidiabetic effect of secoisolariciresinol diglucoside in streptozotocin-induced diabetic rats.