Graduate School of Science and Engineering, Saitama University.
Research Institute for Clinical Oncology, Saitama Cancer Center.
Chem Pharm Bull (Tokyo). 2020;68(12):1123-1130. doi: 10.1248/cpb.c20-00300.
Over the past 30 years, research of green tea polyphenols, especially (-)-epigallocatechin gallate (EGCG), has revealed that consumption of green tea is a practical and effective primary cancer prevention method for the general population. More recently, we believe that green tea polyphenols are beneficial for tertiary cancer prevention using green tea alone or combined with anticancer drugs because EGCG has the potential to inhibit metastatic progression and stemness, and enhance antitumor immunity. In an effort to identify a common underlying mechanism responsible for EGCG's multifunctional effects on various molecular targets, we studied the biophysical effects of EGCG on cell stiffness using atomic force microscopy. We found that EGCG acts to stiffen the membranes of cancer cells, leading to inhibition of signaling pathways of various receptors. Stiffening of membranes with EGCG inhibited AXL receptor tyrosine kinase, a stimulator of cell softening, motility and stemness, and expression of programmed cell death-ligand 1. This review covers the following: i) primary cancer prevention using EGCG or green tea, ii) tertiary cancer prevention by combining EGCG and anticancer drugs, iii) inhibition of metastasis with EGCG by stiffening the cell membrane, iv) inhibition of AXL receptor tyrosine kinase, a stimulator of cell softening and motility, with EGCG, v) inhibition of stemness properties with EGCG, and vi) EGCG as an alternative chemical immune checkpoint inhibitor. Development of new drugs that enhance stiffening of cancer cell membranes may be an effective strategy for tertiary cancer prevention and treatment.
在过去的 30 年中，对绿茶多酚的研究，尤其是（-）-表没食子儿茶素没食子酸酯（EGCG）的研究表明，对于普通人群来说，饮用绿茶是一种实用且有效的一级癌症预防方法。最近，我们认为，单独使用绿茶多酚或与抗癌药物联合使用对三级癌症预防是有益的，因为 EGCG 具有抑制转移进展和干性、增强抗肿瘤免疫的潜力。为了确定 EGCG 对各种分子靶标产生多功能作用的共同潜在机制，我们使用原子力显微镜研究了 EGCG 对细胞刚性的生物物理影响。我们发现，EGCG 作用于使癌细胞的膜变硬，从而抑制各种受体的信号通路。用 EGCG 使膜变硬会抑制 AXL 受体酪氨酸激酶，AXL 受体酪氨酸激酶是细胞软化、运动和干性的刺激物，以及程序性细胞死亡配体 1 的表达。本综述涵盖以下内容：i）使用 EGCG 或绿茶进行一级癌症预防，ii）通过将 EGCG 与抗癌药物联合进行三级癌症预防，iii）通过使细胞膜变硬来抑制转移，iv）用 EGCG 抑制 AXL 受体酪氨酸激酶，一种细胞软化和运动的刺激物，v）用 EGCG 抑制干性特性，以及 vi）EGCG 作为替代化学免疫检查点抑制剂。开发增强癌细胞膜变硬的新药可能是三级癌症预防和治疗的有效策略。
