A putrescine–anthracene conjugate : a paradigm for selective drug delivery

Increased polyamine concentrations play an important role in the development of cancer at all stages, from initiation through to maintenance of the transformed phenotype. One way cancer cells accumulate increased concentrations of polyamines is by increased uptake of preformed polyamines via their...

Full description

Bibliographic Details
Main Authors:	Palmer, Andrew, Abdul Ghani, Radiah, Kaur, Navneet, Phanstiel, Otto, Wallace, Heather
Format:	Article
Language:	English
Published:	BJ Immediate Publication, Great Britain 2009
Subjects:	RM300 Drugs and their action
Online Access:	http://irep.iium.edu.my/27746/ http://irep.iium.edu.my/27746/ http://irep.iium.edu.my/27746/ http://irep.iium.edu.my/27746/1/paper1.pdf

id	iium-27746
recordtype	eprints
spelling	iium-277462012-12-31T08:23:20Z http://irep.iium.edu.my/27746/ A putrescine–anthracene conjugate : a paradigm for selective drug delivery Palmer, Andrew Abdul Ghani, Radiah Kaur, Navneet Phanstiel, Otto Wallace, Heather RM300 Drugs and their action Increased polyamine concentrations play an important role in the development of cancer at all stages, from initiation through to maintenance of the transformed phenotype. One way cancer cells accumulate increased concentrations of polyamines is by increased uptake of preformed polyamines via their PTS(polyamine transport system). The PTS is promiscuous and will transport a range of polyamine-based molecules. Therefore it may be that cytotoxic drugs could be attached to polyamine vectors and targeted selectively to cancer cells by utilizing the PTS. The aim of the present study was to investigate the potential of Ant 4, a putrescine–anthracene conjugate, to target cytotoxic agents to human cancer cells as a paradigm for a novel method of selective drug delivery. Ant 4 induced cytotoxicity after only 24 h exposure. Apoptosis was the predominant type of cell death, with mechanistic studies revealing that oxidative stress and DNA damage may have a part to play. For the first time, uptake of Ant 4 via the PTS was demonstrated both directly and indirectly in human cell lines. In addition, Ant 4 significantly reduced putrescine uptake, demonstrating that this conjugate not only used the PTS, but also could successfully compete with its native polyamine for uptake. However, the most interesting finding was the intracellular depletion of the polyamine pools, providing an additional mode of toxicity for Ant 4 and the possibility that this molecule may act as a ‘double-edged sword’: preventing cell growth by delivery of the toxic moiety and by depletion of intracellular polyamine content. BJ Immediate Publication, Great Britain 2009 Article PeerReviewed application/pdf en http://irep.iium.edu.my/27746/1/paper1.pdf Palmer, Andrew and Abdul Ghani, Radiah and Kaur, Navneet and Phanstiel, Otto and Wallace, Heather (2009) A putrescine–anthracene conjugate : a paradigm for selective drug delivery. Biochemical Journal, 424. pp. 431-438. ISSN 10.1042/BJ20090815 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2805923/pdf/bj4240431.pdf 10.1042/BJ20090815
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	RM300 Drugs and their action
spellingShingle	RM300 Drugs and their action Palmer, Andrew Abdul Ghani, Radiah Kaur, Navneet Phanstiel, Otto Wallace, Heather A putrescine–anthracene conjugate : a paradigm for selective drug delivery
description	Increased polyamine concentrations play an important role in the development of cancer at all stages, from initiation through to maintenance of the transformed phenotype. One way cancer cells accumulate increased concentrations of polyamines is by increased uptake of preformed polyamines via their PTS(polyamine transport system). The PTS is promiscuous and will transport a range of polyamine-based molecules. Therefore it may be that cytotoxic drugs could be attached to polyamine vectors and targeted selectively to cancer cells by utilizing the PTS. The aim of the present study was to investigate the potential of Ant 4, a putrescine–anthracene conjugate, to target cytotoxic agents to human cancer cells as a paradigm for a novel method of selective drug delivery. Ant 4 induced cytotoxicity after only 24 h exposure. Apoptosis was the predominant type of cell death, with mechanistic studies revealing that oxidative stress and DNA damage may have a part to play. For the first time, uptake of Ant 4 via the PTS was demonstrated both directly and indirectly in human cell lines. In addition, Ant 4 significantly reduced putrescine uptake, demonstrating that this conjugate not only used the PTS, but also could successfully compete with its native polyamine for uptake. However, the most interesting finding was the intracellular depletion of the polyamine pools, providing an additional mode of toxicity for Ant 4 and the possibility that this molecule may act as a ‘double-edged sword’: preventing cell growth by delivery of the toxic moiety and by depletion of intracellular polyamine content.
format	Article
author	Palmer, Andrew Abdul Ghani, Radiah Kaur, Navneet Phanstiel, Otto Wallace, Heather
author_facet	Palmer, Andrew Abdul Ghani, Radiah Kaur, Navneet Phanstiel, Otto Wallace, Heather
author_sort	Palmer, Andrew
title	A putrescine–anthracene conjugate : a paradigm for selective drug delivery
title_short	A putrescine–anthracene conjugate : a paradigm for selective drug delivery
title_full	A putrescine–anthracene conjugate : a paradigm for selective drug delivery
title_fullStr	A putrescine–anthracene conjugate : a paradigm for selective drug delivery
title_full_unstemmed	A putrescine–anthracene conjugate : a paradigm for selective drug delivery
title_sort	putrescine–anthracene conjugate : a paradigm for selective drug delivery
publisher	BJ Immediate Publication, Great Britain
publishDate	2009
url	http://irep.iium.edu.my/27746/ http://irep.iium.edu.my/27746/ http://irep.iium.edu.my/27746/ http://irep.iium.edu.my/27746/1/paper1.pdf
first_indexed	2023-09-18T20:41:08Z
last_indexed	2023-09-18T20:41:08Z
_version_	1777409372220030976

A putrescine–anthracene conjugate : a paradigm for selective drug delivery

Similar Items