ANTICARCINOGENIC ACTIVITIES OF SULFORAPHANE AND STRUCTURALLY RELATED SYNTHETIC NORBORNYL ISOTHIOCYANATES

被引:630
作者
ZHANG, YS
KENSLER, TW
CHO, CG
POSNER, GH
TALALAY, P
机构
[1] JOHNS HOPKINS UNIV, SCH MED, DEPT PHARMACOL & MOLEC SCI, BALTIMORE, MD 21205 USA
[2] JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT ENVIRONM HLTH SCI, BALTIMORE, MD 21205 USA
[3] JOHNS HOPKINS UNIV, SCH ARTS & SCI, DEPT CHEM, BALTIMORE, MD 21205 USA
关键词
CHEMOPROTECTION; QUINONE REDUCTASE; ENZYME INDUCTION; DIMETHYLBENZANTHRACENE; RAT MAMMARY TUMORS;
D O I
10.1073/pnas.91.8.3147
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Sulforaphane [1-isothiocyanato-4-(methylsulfinyl) butane] was recently isolated from one variety of broccoli as the major and very potent inducer of phase 2 detoxication enzymes in murine hepatoma cells in culture. Since phase 2 enzyme induction is often associated with reduced susceptibility of animals and their cells to the toxic and neoplastic effects of carcinogens and other electrophiles, it was important to establish whether sulforaphane could block chemical carcinogenesis. In this paper we report that sulforaphane and three synthetic analogues, designed as potent phase 2 enzyme inducers, block the formation of mammary tumors in Sprague-Dawley rats treated with single doses of 9,10-dimethyl-1,2-benzanthracene. The analogues are exo-2-acetyl-exo-6-isothiocyanatonorbornane, endo-2-acetyl-exo-6-isothiocyanatonorboniane, and exo-2-acetyl-exo-5-isothiocyanatonorbornane. When sulforaphane and exo-2-acetyl-exo-6-isothiocyanatonorbornane were administered by gavage (75 or 150 mumol per day for 5 days) around the time of exposure to the carcinogen, the incidence, multiplicity, and weight of mammary tumors were significantly reduced, and their development was delayed. The analogues endo-2-acetyl-exo-6-isothiocyanatonorbornane and exo-2-acetyl-exo-5-isothiocyanatonorbornane were less potent protectors. Thus, a class of functionalized isothiocyanates with anticarcinogenic properties has been identified. These results validate the thesis that inducers of phase 2 enzymes in cultured cells are likely to protect against carcinogenesis.
引用
收藏
页码:3147 / 3150
页数:4
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