Vitamin A Enhances Antitumor Effect of a Green Tea Polyphenol on Melanoma by Upregulating the Polyphenol Sensing Molecule 67-kDa Laminin Receptor
Vitamin A Enhances Antitumor Effect of a Green Tea Polyphenol on Melanoma by Upregulating the Polyphenol Sensing Molecule 67-kDa Laminin Receptor
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DOI：
10.1371/journal.pone.0011051
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发表时间：
2010-06-10
期刊：
影响因子：
3.7
通讯作者：
Tachibana, Hirofumi
中科院分区：
文献类型：
--
作者：
Lee, Ju Hye;Kishikawa, Mutsumi;Tachibana, Hirofumi
背景：饮用绿茶已被证明具有预防癌症的功效。绿茶的成分中，(-)-表没食子儿茶素-3-O-没食子酸酯（EGCG）抑制癌变最有效。然而，在多种癌细胞类型中引发抗癌作用所需的 EGCG 浓度远高于饮用相当于 2-3 杯绿茶后出现的血浆峰值浓度。为了了解日常生活中以合理浓度食用 EGCG 时的抗癌作用，我们研究了 EGCG 和可能增强 EGCG 抗癌活性的食品成分对 B16 黑色素瘤细胞攻击的 C57BL/6N 小鼠皮下肿瘤生长的联合作用。方法/主要发现：全反式视黄酸 (ATRA) 增强 67-kDa 层粘连蛋白受体 (67LR) 的表达并增加 EGCG 诱导的皮下肿瘤生长。 B16 黑色素瘤细胞的细胞生长抑制。 EGCG 和 ATRA 联合治疗所见的细胞生长抑制通过抗 67LR 抗体治疗而消除。此外，EGCG 和 ATRA 联合治疗显着抑制了小鼠黑色素瘤的生长。口服ATRA或EGCG和ATRA联合治疗后，肿瘤中67LR的表达增加。此外，RNAi介导的视黄酸受体（RAR）α沉默减弱了ATRA诱导的黑色素瘤细胞中67LR表达的增强。 RAR 激动剂增强了 67LR 的表达水平，并增加了 EGCG 诱导的细胞生长抑制。结论/意义：我们的研究结果为与膳食成分的组合效应提供了分子基础，并表明 ATRA 与 EGCG 组合时可能是预防癌症的有益食物成分。
Background: Green tea consumption has been shown to have cancer preventive qualities. Among the constituents of green tea, (-)-Epigallocatechin-3-O-gallate (EGCG) is the most effective at inhibiting carcinogenesis. However, the concentrations of EGCG that are required to elicit the anticancer effects in a variety of cancer cell types are much higher than the peak plasma concentration that occurs after drinking an equivalent of 2-3 cups of green tea. To obtain the anticancer effects of EGCG when consumed at a reasonable concentration in daily life, we investigated the combination effect of EGCG and food ingredient that may enhance the anticancer activity of EGCG on subcutaneous tumor growth in C57BL/6N mice challenged with B16 melanoma cells.Methodology/Principal Findings: All-trans-retinoic acid (ATRA) enhanced the expression of the 67-kDa laminin receptor (67LR) and increased EGCG-induced cell growth inhibition in B16 melanoma cells. The cell growth inhibition seen with the combined EGCG and ATRA treatment was abolished by treatment with an anti-67LR antibody. In addition, the combined EGCG and ATRA treatment significantly suppressed the melanoma tumor growth in mice. Expression of 67LR in the tumor increased upon oral administration of ATRA or a combined treatment of EGCG and ATRA treatment. Furthermore, RNAi-mediated silencing of the retinoic acid receptor (RAR) alpha attenuated the ATRA-induced enhancement of 67LR expression in the melanoma cells. An RAR agonist enhanced the expression levels of 67LR and increased EGCG-induced cell growth inhibition.Conclusions/Significance: Our findings provide a molecular basis for the combination effect seen with dietary components, and indicate that ATRA may be a beneficial food component for cancer prevention when combined with EGCG.