Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA, 90059, USA; Center for Human Nutrition, University of California, Los Angeles, CA, 90095, USA.
J Nutr Biochem. 2014 Jan;25(1):73-80. doi: 10.1016/j.jnutbio.2013.09.005. Epub 2013 Oct 10.
The chemopreventive activity of green tea (GT) is limited by the low bioavailability and extensive methylation of GT polyphenols (GTPs) in vivo. We determined whether a methylation inhibitor quercetin (Q) will enhance the chemoprevention of prostate cancer in vivo. Androgen-sensitive LAPC-4 prostate cancer cells were injected subcutaneously into severe combined immunodeficiency (SCID) mice one week before the intervention. The concentration of GTPs in brewed tea administered as drinking water was 0.07% and Q was supplemented in diet at 0.2% or 0.4%. After 6-weeks of intervention tumor growth was inhibited by 3% (0.2% Q), 15% (0.4% Q), 21% (GT), 28% (GT+0.2% Q) and 45% (GT+0.4% Q) compared to control. The concentration of non-methylated GTPs was significantly increased in tumor tissue with GT+0.4% Q treatment compared to GT alone, and was associated with a decreased protein expression of catechol-O-methyltransferase and multidrug resistance-associated protein (MRP)-1. The combination treatment was also associated with a significant increase in the inhibition of proliferation, androgen receptor and phosphatidylinositol 3-kinase/Akt signaling, and stimulation of apoptosis. The combined effect of GT+0.4% Q on tumor inhibition was further confirmed in another experiment where the intervention started prior to tumor inoculation. These results provide a novel regimen by combining GT and Q to improve chemoprevention in a non-toxic manner and warrant future studies in humans.
绿茶（GT）的化学预防活性受到其在体内生物利用度低和广泛甲基化的限制。我们确定甲基化抑制剂槲皮素（Q）是否会增强体内前列腺癌的化学预防作用。雄激素敏感的 LAPC-4 前列腺癌细胞在皮下注射到严重联合免疫缺陷（SCID）小鼠中一周前进行干预。在饮用水中给予的酿造茶中 GT 多酚（GTP）的浓度为 0.07%，Q 以 0.2%或 0.4%的剂量添加到饮食中。干预 6 周后，与对照组相比，饮用水中添加 0.2%Q 可抑制肿瘤生长 3%，添加 0.4%Q 可抑制肿瘤生长 15%，添加 GT 可抑制肿瘤生长 21%，添加 GT+0.2%Q 可抑制肿瘤生长 28%，添加 GT+0.4%Q 可抑制肿瘤生长 45%。与单独使用 GT 相比，GT+0.4%Q 处理可显著增加肿瘤组织中非甲基化 GTP 的浓度，并与儿茶酚-O-甲基转移酶和多药耐药相关蛋白 1（MRP-1）的蛋白表达降低有关。联合治疗还与增殖、雄激素受体和磷脂酰肌醇 3-激酶/ Akt 信号的抑制以及细胞凋亡的刺激显著增加有关。在另一个实验中，在肿瘤接种前开始干预，进一步证实了 GT+0.4%Q 对肿瘤抑制的联合作用。这些结果提供了一种新的方案，通过结合 GT 和 Q 以非毒性方式改善化学预防，并值得在人类中进行进一步研究。
