Yamamoto Tetsuya, Hsu Stephen, Lewis Jill, Wataha John, Dickinson Douglas, Singh Baldev, Bollag Wendy B, Lockwood Petra, Ueta Eisaku, Osaki Tokio, Schuster George
Kochi Medical School, Japan.
J Pharmacol Exp Ther. 2003 Oct;307(1):230-6. doi: 10.1124/jpet.103.054676. Epub 2003 Sep 3.
Green tea polyphenols (GTPPs) are considered beneficial to human health, especially as chemopreventive agents. Recently, cytotoxic reactive oxygen species (ROS) were identified in tumor and certain normal cell cultures incubated with high concentrations of the most abundant GTPP, (-)-epigallocatechin-3-gallate (EGCG). If EGCG also provokes the production of ROS in normal epithelial cells, it may preclude the topical use of EGCG at higher doses. The current study examined the oxidative status of normal epithelial, normal salivary gland, and oral carcinoma cells treated with EGCG, using ROS measurement and catalase and superoxide dismutase activity assays. The results demonstrated that high concentrations of EGCG induced oxidative stress only in tumor cells. In contrast, EGCG reduced ROS in normal cells to background levels. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and 5-bromodeoxyuridine incorporation data were also compared between the two oral carcinoma cell lines treated by EGCG, which suggest that a difference in the levels of endogenous catalase activity may play an important role in reducing oxidative stress provoked by EGCG in tumor cells. It is concluded that pathways activated by GTPPs or EGCG in normal epithelial versus tumor cells create different oxidative environments, favoring either normal cell survival or tumor cell destruction. This finding may lead to applications of naturally occurring polyphenols to enhance the effectiveness of chemo/radiation therapy to promote cancer cell death while protecting normal cells.
绿茶多酚（GTPPs）被认为对人体健康有益，尤其是作为化学预防剂。最近，在与高浓度最丰富的GTPP（-）-表没食子儿茶素-3-没食子酸酯（EGCG）孵育的肿瘤细胞和某些正常细胞培养物中，发现了具有细胞毒性的活性氧（ROS）。如果EGCG也能在正常上皮细胞中引发ROS的产生，那么它可能会排除高剂量EGCG的局部使用。本研究使用ROS测量以及过氧化氢酶和超氧化物歧化酶活性测定，检测了用EGCG处理的正常上皮细胞、正常唾液腺细胞和口腔癌细胞的氧化状态。结果表明，高浓度的EGCG仅在肿瘤细胞中诱导氧化应激。相反，EGCG将正常细胞中的ROS降低至背景水平。还比较了EGCG处理的两种口腔癌细胞系之间的3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐测定和5-溴脱氧尿苷掺入数据，这表明内源性过氧化氢酶活性水平的差异可能在降低EGCG在肿瘤细胞中引发的氧化应激方面发挥重要作用。得出的结论是，GTPPs或EGCG在正常上皮细胞与肿瘤细胞中激活的途径会产生不同的氧化环境，有利于正常细胞存活或肿瘤细胞破坏。这一发现可能会导致天然多酚的应用，以提高化学/放射治疗促进癌细胞死亡同时保护正常细胞的有效性。
