Inhibitory effect of lingonberry extract on HepG2 cell proliferation, apoptosis, migration, and invasion

Abstract

Lingonberry (Vaccinium vitis-idaea L.) extract contains various active ingredients with strong inhibitory effects on cancer cell growth. HepG2 cells were treated with various concentrations of lingonberry extract, cell inhibition rate was measured by CCK-8 assay, and apoptosis rate by annexin-propidium iodide double-staining assay. The cell cycle was analyzed by flow cytometry, and cell migration and invasion by transwell assay. Real-time reverse transcription-PCR and western blotting were employed to analyze the expression of C-X-C motif chemokine ligand 3 (CXCL3). Ki-67, TUNEL, and transwell assays were used to verify the relationship between CXCL3 expression and cell proliferation, apoptosis, migration, and invasion. The composition of lingonberry extract was: 37.58% cyanidin-3-O-glucoside, 10.96% kaempferol 3-O-arabinoside, 4.52% epicatechin, 4.35% chlorogenic acid, 3.83% catechinic acid, 1.54% isoquercitrin, 1.05% 4-hydroxycinnamon acid, 1.03% cyanidin chloride, 0.85% 2,3-dihydroxybenzoic acid, 0.55% quercetin, 0.36% D-(-)-quininic acid, 0.96% caffeic acid, 0.16% ferulic acid, 0.12% oleanolic acid, and 0.03% ursolic acid. Lingonberry extract inhibited the proliferation of HepG2 cells in a dose-dependent manner. After 48 h exposure to 100 μg/mL extract the inhibition rate and IC50 were 80.89±6.05% and 22.62 μg/mL, respectively. Lingonberry extract promoted late apoptosis in HepG2 cells and arrested the cell cycle at G2/M and S phases. Lingonberry extract also promoted the apoptosis of HepG2 cancer cells, inhibiting their proliferation, migration, and invasion by regulating the expression of CXCL3. This study offers new insight into the antihepatoma activity of lingonberry extract and provides a basis for the development of pilot antitumor drugs.