Oral grape seed extract inhibits prostate tumor growth and progression in TRAMP mice
Oral grape seed extract inhibits prostate tumor growth and progression in TRAMP mice
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DOI：
10.1158/0008-5472.can-07-0295
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发表时间：
2007-06-15
期刊：
影响因子：
11.2
通讯作者：
Agarwal, Chapla
中科院分区：
文献类型：
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作者：
Raina, Komal;Singh, Rana P.;Agarwal, Chapla
前列腺癌的化学预防是控制这种恶性肿瘤的一种替代和潜在的策略。在此，我们评价了葡萄籽提取物(GSE)对转基因小鼠前列腺癌(TRAMP)小鼠前列腺癌的化学预防效果。在4~28周龄的小鼠中，GSE以200 mg/kg体重灌胃。我们的结果显示，饲喂GSE的小鼠的生殖道器官重量显著减轻(46%，P<；0.01)。与对照组相比，饲喂GSE组小鼠的前列腺上皮内瘤变的发生率更高，但腺癌的发生率却显著降低。与对照组相比，GSE组前列腺组织中增殖细胞核抗原阳性细胞数减少了50%(P<；0.001)，增殖细胞核抗原总蛋白水平降低了约50%(P<；0.01)，而细胞凋亡率增加了8倍。此外，GSE显著降低Cyclin 131、Cyclin A和Cyclin E的蛋白水平，分别为84%、96%和89%(P<；0.001)。GSE组大鼠前列腺组织中细胞周期蛋白依赖性激酶2、6和CDc2的蛋白表达也降低了90%以上(P<；0.05)。总之，我们首次发现口服GSE可以抑制TRAMP小鼠前列腺癌的生长和进展，这可能是通过强烈抑制细胞周期和细胞增殖以及增加细胞凋亡来实现的。
Prostate cancer chemoprevention is an alternative and potential strategy to control this malignancy. Herein, we evaluated the chemopreventive efficacy of grape seed extract (GSE) against prostate cancer in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice where animals were fed with GSE by oral gavage at 200 mg/kg body weight dose during 4 to 28 weeks of age. Our results showed a significant reduction (46%, P < 0.01) in the weight of genitourinary tract organs in the GSE-fed mice. The GSE-fed group of mice had a higher incidence of prostatic intraepithelial neoplasia but showed strong reduction in the incidence of adenocarcinoma compared with mice in control group. Prostate tissue from the GSE group showed similar to 50% (P < 0.001) decrease in proliferating cell nuclear antigen (PCNA)-positive cells and 64% (P < 0.01) reduction in total PCNA protein level compared with the control group; however, GSE increased apoptotic cells by 8-fold. Furthermore, GSE strongly decreased the protein levels of cyclin 131, cyclin A, and cyclin E by 84% (P < 0.05), 96% (P < 0.05), and 89% (P < 0.001), respectively. The protein expression of cyclin-dependent kinases 2 and 6 and Cdc2 was also decreased by more than 90% (P < 0.05) in the prostate from the GSE-fed group. Together, for the first time, we identified that oral GSE inhibits prostate cancer growth and progression in TRAMP mice, which could be mediated via a strong suppression of cell cycle progression and cell proliferation and an increase in apoptosis.