Wild berries are part of traditional Nordic diets and are a rich source of phytochemicals, such as polyphenols. Various berry treatments have shown to interfere with cancer progression in vitro and in vivo. Here, we systematically reviewed the anticancer effects of two Nordic wild berries of the Vaccinium genus, lingonberry (Vaccinium vitis-idaea) and bilberry (Vaccinium myrtillus), on digestive tract cancers. The review was conducted according to the PRISMA 2020 guidelines. Searches included four databases: PubMed, Scopus, Web of Science, and CAB abstracts. Publications not written in English, case-reports, reviews, and conference abstracts were excluded. Moreover, studies with only indirect markers of cancer risk or studies with single compounds not derived from lingonberry or bilberry were not included. Meta-analysis was not performed. The majority (21/26) of studies investigated bilberry and colorectal cancer. Experimental studies on colorectal cancer indicated that bilberry inhibited intestinal tumor formation and cancer cell growth. One uncontrolled pilot human study supported the inhibitory potential of bilberry on colorectal cancer cell proliferation. Data from all 10 lingonberry studies suggests potent inhibition of cancer cell growth and tumor formation. In conclusion, in vitro and animal models support the antiproliferative and antitumor effects of various bilberry and lingonberry preparations on digestive tract cancers.

Previous studies indicate that bilberry with high amounts of phenolic compounds can inhibit carcinogenic processes of colorectal cancer in vitro and in vivo. However, no studies have focused on the effects of bilberry on oral cancer. In this study, we aimed to examine the effects of bilberry powder on oral squamous cell carcinoma (OSCC) cells using both in vitro and in vivo assays. The effects of 0, 1, 10, and 25 mg/mL of whole bilberry powder on the viability, proliferation, migration, and invasion of OSCC (HSC-3) cells were examined and compared with 0.01 mg/mL of cetuximab. Two oral keratinocyte cell lines served as controls. Tumor area was analyzed in zebrafish microinjected with HSC-3 cells and treated with 2.5, 10, or 25 µg/mL of bilberry powder. Metastases in the head or tail areas were counted. Bilberry powder inhibited the viability, proliferation, migration, and invasion of HSC-3 cells (p < 0.05), which was more pronounced with higher concentrations. Cetuximab had no effect on HSC-3 cell migration or invasion. Compared to controls, the tumor area in zebrafish treated with bilberry powder (10 and 25 µg/mL) was reduced significantly (p = 0.038 and p = 0.021, respectively), but the number of fish with metastases did not differ between groups. Based on our in vitro and in vivo experiments, we conclude that whole bilberry powder has anti-tumor effects on OSCC cells.

Oral squamous cell carcinoma (OSCC) is a common cancer characterised by high rates of metastasis and mortality. Interleukin‑17C (IL-17C) is expressed by several cell types, including epithelial cells, and signals through the heterodimeric IL-17RE/IL-17RA receptor complex at various mucosal sites. The role of IL-17C in OSCC development and progression remains unexamined; therefore, this study aimed to elucidate its potential involvement. Among 11 OSCC cell lines, OU-OTSCC-7B and UH-SCC-17B exhibited a high transcript expression of IL-17C receptors (IL-17RE and IL-17RA) and were selected for further assays. Proliferation, apoptosis, migration, and invasion assays were conducted in the presence and absence of IL-17C. Using a zebrafish xenograft model, we assessed the in vivo effects of IL-17C. Additionally, we performed RNA sequencing after stimulating UH-SCC-17B cells with IL-17C. IL-17C significantly inhibited the proliferation and migration of UH-SCC-17B cells, but had no effect on OU-OTSCC-7B cells. Moreover, IL-17C reduced the tumour size of UH-SCC-17B cells by approximately 10% in the zebrafish model. RNA sequencing revealed the downregulation of five genes, three of which were mitochondrial genes-MT-CYB, MT-ND1, and MTND2P28-implicated in cancer progression. Gene set enrichment analysis revealed the enrichment of the MYC target and oxidative phosphorylation gene sets following IL-17C treatment. IL-17C appears to play a protective role in some OSCC cells. While this study indicates the potential of using IL-17C as a therapeutic candidate for OSCC patients, its relatively mild and selective effect suggests it may be more effective as part of a combination therapy.