Effects of Coptis extract combined with chemotherapeutic agents on ROS production, multidrug resistance, and cell growth in A549 human lung cancer cells

A549 cells were treated with different doses of COP and BER, combined with 5-FU, CPT, and TAX. Cell viability was measured by an XTT (2,3-bis-(2-methoxy-4- nitro-5-sulfophenyl)-2 H-tetrazolium-5-carboxanilide) assay. Intracellular ROS levels were determined by measuring the oxidative conversion of cell permeable 2′,7′-dichlorofluorescein diacetate to fluorescent dichlorofluorescein. MDR of A549 cells was assessed by rhodamine 123 retention assay.Both COP and BER significantly inhibited A549 cell growth in a dose-dependent manner. Combinations of COP or BER with chemotherapeutic agents (5-FU, CPT, and TAX) exhibited a stronger inhibitory effect on A549 cell growth. In addition, COP and BER increased ROS production and reduced MDR in A549 cells.As potential adjuvants to chemotherapy for non–small cell lung cancer, COP and BER increase ROS production, reduce MDR, and enhance the inhibitory effects of chemotherapeutic agents on A549 cell growth.The herb Coptis (COP) is used to treat “damp heat” syndrome in Chinese medicine [1]. Its major constituent is berberine (BER), an isoquinoline alkaloid [2]. The anticancer effects of COP and BER on both hematological and nonhematological cancers have been well documented [3]. Since 2000, experimental studies have confirmed the cytotoxicity of BER in various cancer cell lines, including YES (esophageal carcinoma) [4], HK1 (nasopharyngeal carcinoma) [5], HeLa (cervical carcinoma) [6], HepG2 (hepatocellular carcinoma) [7]. Our previous studies [9,10] have also shown that COP inhibits the growth of breast cancer cells.Non–small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers, and only responds to 15%–25% single agents and 25%–40% combined chemotherapy [11]. NSCLC is typically resistant to apoptosis induced by standard chemotherapy, which causes excessive levels of reactive oxygen species (ROS), leading to impaired intracellular ionic homeostasis by damaging cellular macromolecules and inducing apoptosis [12].