2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC) is a major active constituent of the buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae), a main ingredient of herbal tea in tropical zones. DMC has been reported to significantly reverse drug resistance in BEL-7402/5-FU cells. Glutathione (GSH) and glutathione S-transferase (GST) play important roles in an efflux system that protects the cells from anticancer drugs. In this study, DMC remarkably decreased the intracellular GSH content and GST activity. Furthermore, DMC suppressed the expression of factor erythroid 2-related factor 2 (Nrf2), prevented Nrf2 nuclear translocation, and inhibited the binding of Nrf2 to the antioxidant response element (ARE). The glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM) were down-regulated by inhibiting Nrf2 with DMC treatment. These results suggested that DMC reduced drug efflux to reverse drug resistance by suppressing the Nrf2/ARE signaling pathway in human hepatocellular carcinoma BEL-7402/5-FU cells.

2'，4'-二羟基-6'-甲氧基-3'，5'-二甲基查尔酮（DMC）是沙枣（Cleistocalyx operculatus）芽的主要活性成分（Roxb。）梅尔。et Perry（Myrtaceae），热带地区凉茶的主要成分。据报道，DMC可显着逆转BEL-7402 / 5-FU细胞的耐药性。谷胱甘肽（GSH）和谷胱甘肽S-转移酶（GST）在外排系统中起重要作用，该系统可保护细胞免受抗癌药物的侵害。在这项研究中，DMC显着降低了细胞内GSH含量和GST活性。此外，DMC抑制了类红细胞因子2相关因子2（Nrf2）的表达，防止了Nrf2核易位，并抑制了Nrf2与抗氧化剂反应元件（ARE）的结合。通过用DMC处理抑制Nrf2，可以下调谷氨酸-半胱氨酸连接酶催化亚基（GCLC）和谷氨酸-半胱氨酸连接酶修饰子（GCLM）。