Comparison of antimelanoma effects of 4-S-cysteaminylphenol and its homologues

被引:20
作者
Inoue, S [1 ]
Hasegawa, K [1 ]
Wakamatsu, K [1 ]
Ito, S [1 ]
机构
[1] Fujita Hlth Univ, Sch Hlth Sci, Aichi 4701192, Japan
关键词
antimelanoma agent; melanoma; phenols; tyrosinase;
D O I
10.1097/00008390-199804000-00002
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
4-S-Cysteaminylphenol (4-S-CAP), a phenolic thioether, has been evaluated for melanocytotoxicity. We have recently shown that dihydro-1,4-benzothiazine-6,7-dione (benzothiazine BQ) is the ultimate toxic metabolite produced by tyrosinase oxidation of 4-S-CAP. In this study we compared the antimelanoma effects of 4-S-CAP and its two homologues, alpha-methyl-4-S-cysteaminylphenol (alpha-Me-4-S-CAP) and 4-S-homocysteaminylphenol (4-S-Homo-CAP). Biochemical experiments showed that upon tyrosinase oxidation alpha-Me-4-S-CAP and 4-S-Homo-CAP also produced homologues of BQ which reacted rapidly with reduced glutathione (GSH) and also inhibited alcohol dehydrogenase, an SH enzyme. In vitro experiments showed that 4-S-CAP and its two homologues were taken up into B16-F1 melanoma cells at comparable rates but that 4-S-Homo-CAP was least effective in GSH deprivation, which was reflected in the low cytotoxicity of this phenol, and that the cytotoxicity of the phenols was tyrosinase dependent, as proved by the negligible effects on B16-G4F cells which have a much lower tyrosinase activity. In vivo experiments showed that direct intratumoral administration of these phenols inhibited the subcutaneous growth of B16 melanoma, with 4-S-Homo-CAP being the least effective, and that indirect intraperitoneal administration of 4-S-CAP inhibited melanoma growth much more effectively than the two homologues. These results indicate that 4-S-CAP is the most promising antimelanoma agent among the three phenols examined. (C) 1998 Lippincott-Raven Publishers.
引用
收藏
页码:105 / 112
页数:8
相关论文
共 25 条
[1]  
ALENA F, 1990, CANCER RES, V50, P3743
[2]  
ALENA F, 1994, CANCER RES, V54, P2661
[3]  
COOKSEY CJ, 1995, ANTI-CANCER DRUG DES, V10, P119
[4]  
HASEGAWA K, 1997, BIOCHEM PHARMACOL, V53, P1433
[5]   THE ENANTIOMERIC SPECIFICITY OF THE ANTIHYPERTENSIVE ACTIVITY OF 1-(PHENYLTHIO)-2-AMINOPROPANE, A SYNTHETIC SUBSTRATE-ANALOG FOR DOPAMINE BETA-MONOOXYGENASE [J].
HERMAN, HH ;
HUSAIN, PA ;
COLBERT, JE ;
SCHWERI, MM ;
POLLOCK, SH ;
FOWLER, LC ;
MAY, SW .
JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (03) :1082-1085
[6]   DEMONSTRATION OF THE POTENT ANTIHYPERTENSIVE ACTIVITY OF PHENYL-2-AMINOETHYL SULFIDES [J].
HERMAN, HH ;
POLLOCK, SH ;
FOWLER, LC ;
MAY, SW .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1988, 11 (05) :501-510
[7]   DETERMINATION OF NATURAL THIOLS BY LIQUID-CHROMATOGRAPHY AFTER DERIVATIZATION WITH 3,5-DI-TERT-BUTYL-1,2-BENZOQUINONE [J].
IMAI, Y ;
ITO, S ;
FUJITA, K .
JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS, 1987, 420 (02) :404-410
[8]   MECHANISM OF GROWTH-INHIBITION OF MELANOMA-CELLS BY 4-S-CYSTEAMINYLPHENOL AND ITS ANALOGS [J].
INOUE, S ;
ITO, S ;
WAKAMATSU, K ;
JIMBOW, K ;
FUJITA, K .
BIOCHEMICAL PHARMACOLOGY, 1990, 39 (06) :1077-1083
[9]   MICROANALYSIS OF EUMELANIN AND PHEOMELANIN IN HAIR AND MELANOMAS BY CHEMICAL DEGRADATION AND LIQUID-CHROMATOGRAPHY [J].
ITO, S ;
FUJITA, K .
ANALYTICAL BIOCHEMISTRY, 1985, 144 (02) :527-536
[10]  
ITO S, 1987, BIOCHEM PHARMACOL, V36, P2007