Garlic constituent diallyl trisulfide prevents development of poorly differentiated prostate cancer and pulmonary metastasis multiplicity in TRAMP mice.
Garlic constituent diallyl trisulfide prevents development of poorly differentiated prostate cancer and pulmonary metastasis multiplicity in TRAMP mice.
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DOI：
10.1158/0008-5472.can-08-1677
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发表时间：
2008-11-15
期刊：
影响因子：
11.2
通讯作者：
Dhir R
中科院分区：
文献类型：
--
作者：
Singh SV;Powolny AA;Stan SD;Xiao D;Arlotti JA;Warin R;Hahm ER;Marynowski SW;Bommareddy A;Potter DM;Dhir R
非常需要鉴定无毒但可以延迟前列腺癌（其是美国男性癌症相关死亡的第二大原因）的发作和/或进展的药剂。我们现在证明，口服灌胃大蒜成分二烯丙基三硫化物（1和2毫克/天，每周三次，从8周龄开始，持续13周）显着抑制小鼠前列腺转基因腺癌（TRAMP）小鼠向低分化前列腺癌和肺转移多样性的进展，而没有任何副作用。与对照组相比，1和2 mg DATS处理的小鼠的泌尿生殖道和前列腺的平均湿重有降低的趋势（与对照组相比，DATS处理的小鼠降低了约25-46%）。与对照组小鼠相比，1和2 mg DATS治疗组小鼠的低分化癌发生率和背外侧前列腺所占面积均显著降低。此外，与对照组相比，DATS给药导致肺转移多样性统计学显着降低（P= 0.002）。DATS处理的TRAMP小鼠的背外侧前列腺表现出细胞增殖减少，与细胞周期蛋白B1和securin蛋白水平的诱导相关，并抑制神经内分泌标志物突触素的表达。然而，DATS给药对细胞凋亡诱导、血管生成或自然杀伤细胞和树突状细胞功能没有任何明显影响。总之，本研究的结果首次证明，DATS给药可防止TRAMP小鼠进展为浸润性癌和肺转移。
Identification of agents that are non-toxic but can delay onset and/or progression of prostate cancer, which is the second leading cause of cancer-related deaths among men in the United States, is highly desirable. We now demonstrate that oral gavage of garlic constituent diallyl trisulfide (1 and 2 mg/d, thrice/week for thirteen weeks beginning at eight weeks of age) significantly inhibits progression to poorly-differentiated prostate carcinoma and pulmonary metastasis multiplicity in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice without any side effects. There was a trend of a decrease in average wet weights of the urogenital tract and prostate gland in 1 and 2 mg DATS-treated mice compared with controls (∼25-46% decrease in DATS-treated mice compared with controls). The incidence and the area of the dorsolateral prostate occupied by the poorly-differentiated carcinoma were significantly lower in both 1 and 2 mg DATS-treated mice compared with control mice. In addition, DATS administration resulted in a statistically significant decrease in pulmonary metastasis multiplicity compared with controls (P= 0.002). The dorsolateral prostate from DATS-treated TRAMP mice exhibited decreased cellular proliferation in association with induction of cyclinB1 and securin protein levels, and suppression of the expression of neuroendocrine marker synaptophysin. However, DATS administration did not have any appreciable effect on apoptosis induction, angiogenesis or natural killer and dendritic cell function. In conclusion, the results of the present study demonstrate, for the first time, that DATS administration prevents progression to invasive carcinoma and lung metastasis in TRAMP mice.