Anti-Inflammatory Effects of β-Cryptoxanthin on 5-Fluorouracil-Induced Cytokine Expression in Human Oral Mucosal Keratinocytes

Oral mucositis is a typical adverse effect of chemotherapy, causing oral pain that significantly reduces the patient's quality of life. beta-cryptoxanthin (beta-cry) is a carotenoid abundant in citrus fruits with antioxidant and anti-inflammatory effects. However, the beta-cry effect on oral mucositis remains unclear. We investigated the effects of 5-fluorouracil (5-FU) and beta-cry on human normal oral mucosal keratinocytes (hOMK). hOMK was seeded on a culture plate and cultured with 5-FU and beta-cry. The cell number, mRNA expression of inflammatory cytokines and matrix metalloproteinases (MMPs), and production of inflammatory cytokines in hOMK were evaluated. Additionally, the cell count and inflammatory cytokine production were analyzed when hOMK was co-stimulated with Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) in addition to 5-FU. The numbers of hOMK significantly reduced with 5-FU stimulation, whereas it increased with beta-cry treatment. mRNA expression of interleukin (IL)-6, IL-8, metalloproteinase (MMP)-2, and MMP-9 and protein production of IL-6 and IL-8 in hOMK were augmented on 5-FU stimulation. Simultaneously, beta-cry treatment significantly suppressed IL-8 and MMP-9 mRNA expression, and IL-8 production was induced on 5-FU stimulation. Co-stimulation with P. gingivalis LPS and 5-FU enhanced IL-6 and IL-8 production in hOMK. beta-cry could enhance cell proliferation and suppress 5-FU-induced expression of inflammatory cytokines and MMP in hOMK. Thus, beta-cry can alleviate the symptoms of chemotherapy-induced oral mucositis, and its combination with oral care is effective in managing oral mucositis.

Automated summary

Oral mucositis, a common side effect of chemotherapy, causes oral pain and affects patients' quality of life. The effects of beta-cryptoxanthin (beta-cry), a carotenoid found in citrus fruits with antioxidant and anti-inflammatory properties, on oral mucositis are unclear. In this study, we found that beta-cry can enhance cell proliferation and suppress the expression of inflammatory cytokines and matrix metalloproteinases induced by 5-fluorouracil (5-FU) in human normal oral mucosal keratinocytes (hOMK). These findings suggest that beta-cry can alleviate chemotherapy-induced oral mucositis when combined with oral care.