Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Hakozaki, Japan.
PLoS One. 2010 Jun 10;5(6):e11051. doi: 10.1371/journal.pone.0011051.
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.
绿茶的消费已被证明具有防癌特性。在绿茶的成分中，（-）-表没食子儿茶素-3-O-没食子酸酯（EGCG）在抑制致癌作用方面最为有效。然而，在各种癌细胞类型中，需要达到能够引起抗癌作用的 EGCG 浓度，远高于饮用相当于 2-3 杯绿茶后出现的峰值血浆浓度。为了在日常生活中以合理的浓度摄入 EGCG 获得其抗癌作用，我们研究了 EGCG 与可能增强 EGCG 抗癌活性的食品成分的组合效应，以抑制 C57BL/6N 小鼠皮下接种 B16 黑色素瘤细胞后肿瘤的生长。
方法/主要发现：全反式维甲酸（ATRA）增强了 67-kDa 层粘连蛋白受体（67LR）的表达，并增加了 EGCG 诱导的 B16 黑色素瘤细胞生长抑制。用抗 67LR 抗体处理后，联合 EGCG 和 ATRA 治疗的细胞生长抑制作用被消除。此外，联合 EGCG 和 ATRA 治疗显著抑制了小鼠的黑色素瘤肿瘤生长。在口服 ATRA 或联合 EGCG 和 ATRA 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：我们的研究结果为饮食成分联合作用提供了分子基础，并表明 ATRA 与 EGCG 联合使用可能是一种有益的预防癌症的食品成分。
