Polyamine analogues as anticancer drugs

被引:72
作者
Wallace, HM
Fraser, AV
机构
[1] Univ Aberdeen, Dept Med & Therapeut, Aberdeen AB25 5ZD, Scotland
[2] Univ Aberdeen, Dept Biomed Sci, Aberdeen AB25 5ZD, Scotland
关键词
cancer; chemotherapy; inhibitor; putrescine; spermidine; spermine;
D O I
10.1042/BST0310393
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Just over 30 years ago, the late Diane Russell published the first in a series of papers linking polyamines and cancer. These early studies led to a flurry of research activity in the polyamine field that continues to this day attempting to identify a role for the polyamines in cancer development, treatment and/or prevention. The recognition that polyamines are critical for the growth of cancer cells, and consequently the identification of their metabolic pathways as a target for therapeutic intervention, led to the development of a number of useful inhibitors of polyamine biosynthesis. Arguably the most significant addition to the polyamine field in the last 30 years was the synthesis of alpha-difluoromethylornithine (DFMO), which is being tested currently as a cancer chemopreventative agent in man and is used also as a highly effective trypanocidal agent. Although an extremely useful tool experimentally, DFMO has been disappointing in clinical trials with little therapeutic efficacy. Despite this setback, the polyamine pathway is still considered a viable target for chemotherapeutic intervention. This has led to the development of the polyamine analogues as multifunctional inhibitors that will produce inhibition of tumour cell growth, polyamine depletion and optimum therapeutic efficacy.
引用
收藏
页码:393 / 396
页数:4
相关论文
共 34 条
[1]   BIS(BENZYL)POLYAMINE ANALOGS INHIBIT THE GROWTH OF CHLOROQUINE-RESISTANT HUMAN MALARIA PARASITES (PLASMODIUM-FALCIPARUM) INVITRO AND IN COMBINATION WITH ALPHA-DIFLUOROMETHYLORNITHINE CURE MURINE MALARIA [J].
BITONTI, AJ ;
DUMONT, JA ;
BUSH, TL ;
EDWARDS, ML ;
STEMERICK, DM ;
MCCANN, PP ;
SJOERDSMA, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (02) :651-655
[2]   Terminally alkylated polyamine analogues as chemotherapeutic agents [J].
Casero, RA ;
Woster, PM .
JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (01) :1-26
[3]  
CASERO RA, 1989, CANCER RES, V49, P639
[4]  
CASERO RA, 1989, CANCER RES, V49, P3829
[5]   SPERMIDINE SPERMINE N1-ACETYLTRANSFERASE - THE TURNING-POINT IN POLYAMINE METABOLISM [J].
CASERO, RA ;
PEGG, AE .
FASEB JOURNAL, 1993, 7 (08) :653-661
[6]   AMINOOXY ANALOGS OF SPERMIDINE AS INHIBITORS OF SPERMINE SYNTHASE AND SUBSTRATES OF HEPATIC POLYAMINE ACETYLATING ACTIVITY [J].
ELORANTA, TO ;
KHOMUTOV, AR ;
KHOMUTOV, RM ;
HYVONEN, T .
JOURNAL OF BIOCHEMISTRY, 1990, 108 (04) :593-598
[7]   Induction of apoptosis in human leukaemic cells by IPENSpm, a novel polyamine analogue and anti-metabolite [J].
Fraser, AV ;
Woster, PM ;
Wallace, HM .
BIOCHEMICAL JOURNAL, 2002, 367 (01) :307-312
[8]   POLYAMINES IN RAPID GROWTH AND CANCER [J].
JANNE, J ;
POSO, H ;
RAINA, A .
BIOCHIMICA ET BIOPHYSICA ACTA, 1978, 473 (3-4) :241-293
[9]   CELLULAR CHARACTERIZATION OF A NEW IRREVERSIBLE INHIBITOR OF S-ADENOSYLMETHIONINE DECARBOXYLASE AND ITS USE IN DETERMINING THE RELATIVE ABILITIES OF INDIVIDUAL POLYAMINES TO SUSTAIN GROWTH AND VIABILITY OF L1210 CELLS [J].
KRAMER, DL ;
KHOMUTOV, RM ;
BUKIN, YV ;
KHOMUTOV, AR ;
PORTER, CW .
BIOCHEMICAL JOURNAL, 1989, 259 (02) :325-331
[10]   Changes in polyamine catabolism in HL-60 human promyelogenous leukaemic cells in response to etoposide-induced apoptosis [J].
Lindsay, GS ;
Wallace, HM .
BIOCHEMICAL JOURNAL, 1999, 337 :83-87