Brooks J D, Paton V G, Vidanes G
Department of Urology, Stanford University Medical Center, Stanford, California 94305-5118, USA.
Cancer Epidemiol Biomarkers Prev. 2001 Sep;10(9):949-54.
Two population-based, case-control studies have documented reduced risk of prostate cancer in men who consume cruciferous vegetables. Cruciferae contain high levels of the isothiocyanate sulforaphane. Sulforaphane is known to bolster the defenses of cells against carcinogens through up-regulation of enzymes of carcinogen defense (phase 2 enzymes). Prostate cancer is characterized by an early and near universal loss of expression of the phase 2 enzyme glutathione S-transferase (GST)-pi. We tested whether sulforaphane may act in prostatic cells by increasing phase 2 enzyme expression. The human prostate cancer cell lines LNCaP, MDA PCa 2a, MDA PCa 2b, PC-3, and TSU-Pr1 were treated with 0.1-15 microM sulforaphane in vitro. LNCaP was also treated with an aqueous extract of broccoli sprouts. Quinone reductase enzymatic activity, a surrogate of global phase 2 enzyme activity, was assayed by the menadione-coupled reduction of tetrazolium dye. Expression of NQO-1, GST-alpha, gamma-glutamylcysteine synthetase-heavy and -light chains, and microsomal GST was assessed by Northern blot analysis. Sulforaphane and broccoli sprout extract potently induce quinone reductase activity in cultured prostate cells, and this induction appears to be mediated by increased transcription of the NQO-1 gene. Sulforaphane also induces expression of gamma-glutamylcysteine synthetase light subunit but not the heavy subunit, and this induction is associated with moderate increases in intracellular glutathione levels. Microsomal and alpha-class glutathione transferases were also induced transcriptionally. Sulforaphane induces phase 2 enzyme expression and activity significantly in human prostatic cells. This induction is accompanied by, but not because of, increased intracellular glutathione synthesis. Our findings may help explain the observed inverse correlation between consumption of cruciferae and prostate cancer risk.
两项基于人群的病例对照研究表明，食用十字花科蔬菜的男性患前列腺癌的风险降低。十字花科植物含有高水平的异硫氰酸酯萝卜硫素。已知萝卜硫素通过上调致癌物防御酶（二期酶）来增强细胞对致癌物的防御能力。前列腺癌的特征是二期酶谷胱甘肽S-转移酶（GST）-pi的表达早期且几乎普遍丧失。我们测试了萝卜硫素是否可能通过增加二期酶的表达在前列腺细胞中发挥作用。在体外，用0.1 - 15微摩尔的萝卜硫素处理人前列腺癌细胞系LNCaP、MDA PCa 2a、MDA PCa 2b、PC-3和TSU-Pr1。LNCaP也用西兰花芽苗的水提取物处理。通过甲萘醌偶联的四唑染料还原法测定醌还原酶的酶活性，作为整体二期酶活性的替代指标。通过Northern印迹分析评估NQO-1、GST-α、γ-谷氨酰半胱氨酸合成酶重链和轻链以及微粒体GST的表达。萝卜硫素和西兰花芽苗提取物能有效诱导培养的前列腺细胞中的醌还原酶活性，这种诱导似乎是由NQO-1基因转录增加介导的。萝卜硫素还诱导γ-谷氨酰半胱氨酸合成酶轻亚基的表达，但不诱导重亚基的表达，这种诱导与细胞内谷胱甘肽水平的适度增加有关。微粒体和α类谷胱甘肽转移酶也被转录诱导。萝卜硫素在人前列腺细胞中显著诱导二期酶的表达和活性。这种诱导伴随着细胞内谷胱甘肽合成的增加，但不是由其引起的。我们的发现可能有助于解释观察到的十字花科植物消费与前列腺癌风险之间的负相关关系。
