Effects of β-Cryptoxanthin on Cisplatin-Treated Human Oral Mucosa-Derived Keratinocytes and Fibroblasts

Cisplatin (CDDP) is an anticancer drug that is frequently used to treat head and neck cancers; however, it may cause oral mucositis. The discontinuation of CDDP may be required for some patients with a severe status, and the control of oral mucositis is extremely important. β-Cryptoxanthin (β-cry), a carotenoid, exerts anti-inflammatory effects. Its inhibition of 5-FU-induced inflammatory responses was recently demonstrated. However, the effects of β-cry on CDDP-induced oral mucositis remain unclear. In the present study, we stimulated human oral mucosa-derived keratinocytes (hOMK) and fibroblasts (hOMF) with CDDP, added β-cry, and examined its effects, with a focus on the production of inflammatory cytokines, matrix metalloproteinase (MMPs), and reactive oxygen species (ROS). CDDP increased the mRNA expression and production of inflammatory cytokines and MMPs both in hOMK and hOMF. However, increases in IL-6 and MMP-9 mRNA expression levels and IL-6 production in CDDP-treated hOMK and hOMF were inhibited by β-cry. Furthermore, the production of ROS and the rate of SA-β-gal-positive cells were increased by CDDP, but were not affected by β-cry. CDDP may induce oral mucositis by increasing the levels of inflammatory cytokines, MMPs, and ROS. β-cry partially inhibited CDDP-induced increases in inflammatory cytokines and MMPs, suggesting its potential to attenuate the symptoms of chemotherapy-related oral mucositis.