The Bowman-Birk inhibitor from soybeans as an anticarcinogenic agent
The Bowman-Birk inhibitor from soybeans as an anticarcinogenic agent
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DOI：
10.1093/ajcn/68.6.1406s
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发表时间：
1998-12-01
影响因子：
7.1
通讯作者：
Kennedy, AR
中科院分区：
文献类型：
--
作者：
Kennedy, AR
某些蛋白酶抑制剂在体外预防或抑制致癌物诱导的转化和动物模型系统的致癌作用方面是有效的。一种蛋白酶抑制剂，大豆衍生的鲍曼-伯克抑制剂（BBI）在抑制癌变方面特别有效。BBI是一种分子量为8000的蛋白质，具有良好的抑制胰蛋白酶和凝乳胰蛋白酶的能力。BBI已被广泛研究，无论是作为纯化BBI还是作为富含BBI的大豆提取物BBI浓缩物（BBIC）。纯化BBI和BBIC对多种体内和体外系统的致癌过程具有相当的抑制作用。BBI似乎是一种普遍的癌症预防剂。纯化BBI和BBIC对3种不同物种（小鼠、大鼠和仓鼠）的抗癌作用如下；在一些器官系统和组织类型中[例如，结肠、肝脏、肺、食道、颊袋（口腔上皮）和造血细胞]；在上皮和结缔组织起源的细胞中，通过几种不同的给药途径，包括饮食，导致不同类型的癌症（如鳞状细胞癌、腺癌和血管肉瘤），并被各种化学和物理致癌物诱导。大约一半的口服剂量的BBI被吸收到血液中并分布在全身，通过尿液排泄。BBI的药代动力学研究已在放射性标记BBI的动物中进行，而与还原BBI反应的抗体正在用于人类的药代动力学研究。计算的血清半衰期在大鼠和仓鼠均为10小时。BBIC于1992年4月获得FDA的新药研究资格(IND号：34671年;赞助商，Ann R Kennedy)，并开始了评估BBIC在人群中作为抗癌剂的研究。BBI和BBIC在体外均能预防和抑制恶性转化和体内癌变，且无毒性。
Certain protease inhibitors are effective at preventing or suppressing carcinogen-induced transformation in vitro and carcinogenesis in animal model systems. One protease inhibitor, the soybean-derived Bowman-Birk inhibitor (BBI) is particularly effective in suppressing carcinogenesis. BBI is a protein of a molecular weight of 8000 with a well-characterized ability to inhibit trypsin and chymotrypsin. BBI has been extensively studied, both as purified BBI and as an extract of soybeans enriched in BBI called BBI concentrate (BBIC). Purified BBI and BBIC have comparable suppressive effects on the carcinogenic process in a variety of in vivo and in vitro systems. BBI appears to be a universal cancer preventive agent. Purified BBI and BBIC suppress carcinogenesis as follows: in 3 different species (mice, rats, and hamsters); in several organ systems and tissue types [eg, colon, liver, lung, esophagus, cheek pouch (oral epithelium), and cells of hematopoietic origin]; and in cells of epithelial and connective tissue origin when given to animals by several different routes of administration, including the diet, leading to different types of cancer (eg, squamous cell carcinomas, adenocarcinomas, and angiosarcomas), and induced by various chemical and physical carcinogens. About half of an oral dose of BBI is taken up into the bloodstream and distributed throughout the body, with excretion via the urine. Pharmacokinetic studies of BBI have been performed in animals with radioactively labeled BBI, whereas antibodies that react with reduced BBI are being used in pharmacokinetic studies in humans. The calculated serum half-life is 10 h in both rats and hamsters. BBIC achieved Investigational New Drug status from the FDA in April 1992 (IND no. 34671; sponsor, Ann R Kennedy), and studies to evaluate BBIC as an anticarcinogenic agent in human populations began. Both BBI and BBIC prevent and suppress malignant transformation in vitro and carcinogenesis in vivo without toxicity.