Cold-pressed lingonberry (Vaccinium vitis-idaea) extract inhibits proliferation and invasion of oral carcinoma cells and modulates cellular energy metabolism

Background Berry phytochemicals show anticancer effects and may reduce the progression of oral carcinoma. One possible target is the differential energy metabolism of transformed cells. We investigated the anticancer activity of cold-pressed lingonberry extract (LBE) on oral squamous cell carcinoma (OSCC). Methods Cells were treated with LBE (0.1%, 1% and 2%) or control in culture media, with and without pH-adjustment. Four oral cell lines were tested for proliferation after 72 h; primary oral tongue (SCC-25) and metastatic lymph node oral tongue (HSC-3) squamous cell carcinomas, HPV-16 immortalized oral keratinocytes (IHGK) and normal oral fibroblasts (NOF). Additionally, proliferation and apoptosis of the malignant cell lines were investigated over 48 h with live cell imaging, and invasion of HSC-3 over 72 h in a spheroid model. Cellular glycolysis and mitochondrial respiration were measured after 48 h of LBE pretreatment in all 4 cell lines. Results LBE inhibited proliferation of the OSCC cells, but not NOF. Native and pH-adjusted LBEs similarly reduced invasion, but the native LBE had a pronounced effect on proliferation. IHGK was significantly inhibited only with the native LBE. pH-adjusted LBE increased apoptosis in HSC-3. Along with proliferation, both extracts inhibited glycolysis in the OSCC cells but had no effect on NOF. LBE increased mitochondrial respiration in the malignant but decreased it in the IHGK and NOF cells. Conclusions Lingonberry extract inhibited proliferation and invasion of OSCC, possibly by targeting the differential cellular energy metabolism of transformed cells. The results indicate that lingonberry could have significance in the prevention and in the inhibition of progression of oral carcinoma.