Regional Cancer Institute, Chungnam National University Hospital, Daejeon 301-721, Republic of Korea.
Phytother Res. 2011 Jun;25(6):833-7. doi: 10.1002/ptr.3323. Epub 2010 Nov 19.
Inactivation of epidermal growth factor receptor (EGFR) is a prime method used in colon cancer therapy. Here it is shown that chrysophanic acid, a natural anthraquinone, has anticancer activity in EGFR-overexpressing SNU-C5 human colon cancer cells. Chrysophanic acid preferentially blocked proliferation in SNU-C5 cells but not in other cell lines (HT7, HT29, KM12C, SW480, HCT116 and SNU-C4) with low levels of EGFR expression. Chrysophanic acid treatment in SNU-C5 cells inhibited EGF-induced phosphorylation of EGFR and suppressed activation of downstream signaling molecules, such as AKT, extracellular signal-regulated kinase (ERK) and the mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase (p70S6K). Chrysophanic acid (80 and 120 µm) significantly blocked cell proliferation when combined with the mTOR inhibitor, rapamycin. These findings offer the first evidence of anticancer activity for chrysophanic acid via EGFR/mTOR mediated signaling transduction pathway.
表皮生长因子受体 (EGFR) 的失活是结肠癌治疗的主要方法。本文显示，天然蒽醌类化合物大黄酸对 EGFR 过表达的 SNU-C5 人结肠癌细胞具有抗癌活性。大黄酸优先阻断 SNU-C5 细胞的增殖，但对其他细胞系（HT7、HT29、KM12C、SW480、HCT116 和 SNU-C4）没有作用，这些细胞系 EGFR 表达水平较低。大黄酸处理 SNU-C5 细胞可抑制 EGF 诱导的 EGFR 磷酸化，并抑制下游信号分子如 AKT、细胞外信号调节激酶 (ERK) 和雷帕霉素靶蛋白 (mTOR)/核糖体蛋白 S6 激酶 (p70S6K) 的激活。大黄酸 (80 和 120 µm) 与 mTOR 抑制剂雷帕霉素联合使用时，可显著抑制细胞增殖。这些发现为大黄酸通过 EGFR/mTOR 介导的信号转导通路发挥抗癌活性提供了首个证据。
