Abstract
BackgroundNon–small cell lung cancer is associated with high expression of multidrug resistance (MDR) proteins and low production of reactive oxygen species (ROS). Coptis extract (COP), a Chinese medicinal herb, and its major constituent, berberine (BER), have anticancer properties. This study aims to investigate the effects of COP and BER combined with chemotherapeutic agents, including fluorouracil (5-FU), camptothecin (CPT), and paclitaxel (TAX), on cell proliferation, ROS production, and MDR in A549 human non-small cell lung cancer cells.MethodsA549 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.ResultsBoth 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.ConclusionAs 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.
Highlights
Non–small cell lung cancer is associated with high expression of multidrug resistance (MDR) proteins and low production of reactive oxygen species (ROS)
This study aims to investigate the effects of Coptis extract (COP) and BER on ROS production and MDR, and the effects of combinations of COP or BER with chemotherapeutic agents, including fluorouracil (5-FU), camptothecin (CPT), and paclitaxel (TAX) on A549 human cancer cells, which are derived from Non–small cell lung cancer (NSCLC) [18]
A Pearson Correlation Test by Prism 4 was used to determine the correlation between the doses of COP or BER and the inhibitory effects on A549 cell growth
Summary
Non–small cell lung cancer is associated with high expression of multidrug resistance (MDR) proteins and low production of reactive oxygen species (ROS). Coptis extract (COP), a Chinese medicinal herb, and its major constituent, berberine (BER), have anticancer properties. This study aims to investigate the effects of COP and BER combined with chemotherapeutic agents, including fluorouracil (5-FU), camptothecin (CPT), and paclitaxel (TAX), on cell proliferation, ROS production, and MDR in A549 human non-small cell lung cancer cells. 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]. In addition to ROS, multidrug-resistance (MDR) proteins are intrinsically expressed and functionally active in NSCLC cells [14]. Several adjuvants to chemotherapy for NSCLC are being tested, with promising results, including the antagonists of EGFR and COX-2 [15,16,17]
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