Trimethoxy-Resveratrol and Piceatannol Administered Orally Suppress and Inhibit Tumor Formation and Growth in Prostate Cancer Xenografts
Trimethoxy-Resveratrol and Piceatannol Administered Orally Suppress and Inhibit Tumor Formation and Growth in Prostate Cancer Xenografts
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DOI：
10.1002/pros.22657
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发表时间：
2013-08-01
期刊：
影响因子：
2.8
通讯作者：
Levenson, Anait S.
中科院分区：
文献类型：
--
作者：
Dias, Steven J.;Li, Kun;Levenson, Anait S.
背景白藜芦醇（Resveratrol，Res）具有抗氧化、抗炎、抗癌等特性，是一种很有前途的癌症化学预防膳食多酚。然而，其类似物在前列腺癌（PCa）化学预防中的作用尚不清楚。我们合成了几种天然的和合成的类似物的RES和其特征在于在体外使用细胞增殖试验对PCa细胞的影响。对随后用于体内研究的LNCaP-Luc细胞进行集落形成测定和荧光素酶（Luc）活性的体外验证。在皮下（s.c.）PCa模型。通过传统卡尺和生物发光成像监测肿瘤进展。ELISA法检测血清中细胞因子水平，气相色谱-质谱法检测血清和肿瘤组织中化合物水平。我们研究了Res/类似物在三种PCa细胞系中的抗增殖活性。我们进一步比较了口服Res、3 M-Res和PIC在LNCaP-Luc异种移植物中的化学预防作用。我们发现，用化合物预处理2周减少了异种移植物中的细胞定植，减小了肿瘤体积，并降低了肿瘤生长。3 M-Res和PIC对肿瘤生长的抑制作用均优于Res，其中3 M-Res对肿瘤细胞增殖和集落形成的抑制作用最强，在血清和肿瘤组织中的蓄积量最高。我们的研究结果提供了强有力的临床前证据，利用膳食芪，特别是3 M-Res，作为新的，强大的，有效的化学预防剂在前列腺癌。(C)2013 Wiley Periodicals，Inc.
BACKGROUND. Resveratrol (Res) is recognized as a promising cancer chemoprevention dietary polyphenol with antioxidative, anti-inflammatory, and anticancer properties. However, the role of its analogues in prostate cancer (PCa) chemoprevention is unknown.METHODS. We synthesized several natural and synthetic analogues of Res and characterized their effects on PCa cells in vitro using a cell proliferation assay. A colony formation assay and in vitro validation of luciferase (Luc) activity was done for LNCaP-Luc cells that were consequently used for in vivo studies. The efficacy of Res, trimethoxy-resveratrol (3M-Res) and piceatannol (PIC) was studied in a subcutaneous (s.c.) model of PCa using oral gavage. Tumor progression was monitored by traditional caliper and bioluminescent imaging. The levels of cytokines in serum were examined by ELISA, and the levels of compounds in serum and tumor tissues were determined by gas chromatography-mass spectrometry.RESULTS. We examined the anti-proliferative activities of Res/analogues in three PCa cell lines. We further compared the chemopreventive effects of oral Res, 3M-Res, and PIC in LNCaP-Luc-xenografts. We found that 2 weeks pretreatment with the compounds diminished cell colonization, reduced tumor volume, and decreased tumor growth in the xenografts. Both 3M-Res and PIC demonstrated higher potency in inhibiting tumor progression compared to Res. Notably, 3M-Res was the most active in inhibiting cell proliferation and suppressing colony formation, and its accumulation in both serum and tumor tissues was the highest.CONCLUSIONS. Our findings offer strong pre-clinical evidence for the utilization of dietary stilbenes, particularly 3M-Res, as novel, potent, effective chemopreventive agents in PCa. (C) 2013 Wiley Periodicals, Inc.