Inhibition of CWR22Rν1 tumor growth and PSA secretion in athymic nude mice by green and black teas
Inhibition of CWR22Rν1 tumor growth and PSA secretion in athymic nude mice by green and black teas
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DOI：
10.1093/carcin/bgi323
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发表时间：
2006-04-01
期刊：
影响因子：
4.7
通讯作者：
Mukhtar, H
中科院分区：
文献类型：
--
作者：
Siddiqui, IA;Zaman, N;Mukhtar, H
前列腺癌（CaP）是美国男性人群中最常见的侵袭性恶性肿瘤，也是癌症相关死亡的主要原因，是化学预防的理想候选疾病，因为它通常在老年人群中检测到，其生长和进展速度相对较慢。至少在CaP的临床前模型中，许多膳食植物化学物质显示出有希望的化学预防作用。我们在细胞培养和动物研究中发表的数据，得到其他实验室工作的支持，以及流行病学观察和病例对照研究，表明绿茶中存在的多酚具有CaP的化学预防作用，并可能具有治疗作用。本研究旨在比较绿茶多酚（GTP）、红茶水提物及其主要成分表没食子儿茶素-3-没食子酸酯和茶黄素分别对雄性激素敏感的人CaP CWR22R nu 1细胞植入胸腺裸鼠的化学预防作用。我们的数据表明，用所有茶叶成分治疗导致(i)显著抑制植入前列腺肿瘤的生长，（ii）降低血清前列腺特异性抗原水平，（iii）诱导细胞凋亡，并伴有Bax上调和Bcl-2蛋白降低，以及（iv） VEGF蛋白水平降低。此外，我们还发现GTP（0.01或0.05% w/v；在CWR22R nu 1肿瘤建立后给出）导致肿瘤显著消退，表明GTP在人类可达到的浓度下具有治疗作用。
Cancer of the prostate gland (CaP), the most common invasive malignancy and a major cause of cancer related deaths in male population in the USA, is an ideal candidate disease for chemoprevention because it is typically detected in elderly population with a relatively slower rate of growth and progression. Many dietary phytochemicals are showing promising chemopreventive effects, at-least in pre-clinical models of CaP. Our published data in cell culture and animal studies, supported by the work from other laboratories, as well as epidemiological observations and case-control studies, suggest that polyphenols present in green tea possess CaP chemopreventive and possibly therapeutic effects. This present study was designed to compare CaP cancer chemopreventive effects of green tea polyphenols (GTP), water extract of black tea, and their major constituents epigallocatechin-3-gallate and theaflavins, respectively, in athymic nude mice implanted with androgen-sensitive human CaP CWR22R nu 1 cells. Our data demonstrated that the treatment with all the tea ingredients resulted in (i) significant inhibition in growth of implanted prostate tumors, (ii) reduction in the level of serum prostate specific antigen, (iii) induction of apoptosis accompanied with upregulation in Bax and decrease in Bcl-2 proteins, and (iv) decrease in the levels of VEGF protein. Furthermore, we also found that GTP (0.01 or 0.05% w/v; given after establishment of CWR22R nu 1 tumor) causes a significant regression of tumors suggesting therapeutic effects of GTP at human achievable concentrations.