Fireweed (Chamerion angustifolium L.) leaf extract: biological properties and effects on mitochondria in colorectal Caco-2 cancer cell lines

Abstract

Introduction. Extracts from fireweed possess anti-inflammatory antioxidant, anti-proliferative, activity [1] due to flavonoids, phenolic acids, ellagitannins found in it. Aim. Since the mitochondria play an important role in cancer and other pathologies, the aim of this study was to investigated the effect of fireweed (Chamerion angustifolium L.) leaves aqueous extract on the cell viability and mitochondrial function in human colorectal adenocarcinoma cancer (Caco-2) cells. Methods. Caco-2 cells were incubated for 24 h in RPMI 1640 medium supplemented with 10% of fetal bovine serum and 1% penicillin/streptomycin at 37 °C in 5% CO2 humidity. Then cells were treated by fireweed (fermented (F) and non-fermented (NF)) leaves aqueous extracts (IC50=1,17 mg/ml and 0.81 mg/ml) for 48 hours (the solid-phase fermentation of fireweed leaves took place at 30 °C for 48 h). Mitochondrial respiration rate was measured using an Oxygraph-2k at 37 °C with two different substrates (glutamate/malate and succinate) [2]. Results. In fireweed aqueous extract oenothein B, elagic, p-coumaric, chlorogenic, neochlorogenic acids, hyperoxide and isoquercitrin were determined by HPLC. The effect of fireweed extract on the Caco-2 cell viability was dose-dependent and caused the decrease in viability by 20-91%. The mitochondrial ADP dependent respiration rate after pre-treatment with fireweed (F and NF) extract decreased by 40% and by 52% (glutamate/malate) and by 27% and 35% (succinate), respectively. The leak respiration rate increased by 62% and 73%, p<0.05, showing the damage of inner mitochondrial membrane. The cytochrome c effect was also slightly increased after pre-treatment of cells with fireweed extract showing the damage of mitochondrial outer membrane. Conclusion. fireweed leaf aqueous extract (from both, fermented and non-fermented leaves) reduces significantly the Caco-2 cell viability and mitochondrial oxidative phosphorylation in Caco-2 cells and might be promissing therapeutic agent in cancer cells.