## 1 Introduction  
Potent treatment approaches, such as the use of high-dose anticancer drugs and combination chemotherapy, have recently been performed to improve the outcomes of cancer treatment. Cisplatin (cis-diamminedichloro-platinum (II), CDDP) is one of the most frequently used anticancer drugs for squamous cell carcinoma, which accounts for the majority of oral cancers, along with 5-FU. The outcomes of multi-drug therapy with CDDP and a target anticancer drug or radiation are favorable, suggesting its utility [1, 2]. However, the side effects of CDDP include nausea, general malaise, nephropathy, pancytopenia, and mucositis [3, 4, 5]. Oral mucositis is a well-known and important side effect of CDDP [6]. The turnover of mucosal epithelial cells comprising the mucosa is fast, and these cells may be readily affected by DNA damage, which ultimately results in cell death or a decrease in regeneration [7, 8]. The inflammatory responses of mucosal epithelial cells to the cytotoxicity of anticancer drugs appear on the surfaces of all elementary canal mucosaefrom the oral cavity to the rectum [3]. The mucosal barrier is destroyed, resulting in or increasing susceptibility to various symptoms [9]. For example, oral mucositis caused by anticancer drugs is commonly observed in the oral cavity: in chemotherapy alone, 30 to 40%; in hematopoietic stem cell transplantation-related high-dose chemotherapy, 70 to 90%. Since oral mucositis markedly affects oral function, its prevention is extremely important [10,11]. Various treatments, such as laser irradiation, local anesthetics, gargling with mouthwash, and cryotherapy, have been employed to control oral mucositis [12, 13, 14, 15]. However, symptomatic treatment is currently the primary therapeutic approach, and its effects remain insufficient. Therefore, the establishment of effective prevention/treatment methods is needed.  
\(\beta\)-Cryptoxanthin (\(\beta\)-cry) is a pigment component of mandarin oranges, persimmons, and oranges, and is also present in chili pepper and paprika as a carotenoid. It is converted to vitamin A in vivo, which maintains physical functions and exerts inhibitory effects on carcinogenesis, exhibits DNA-repairing activity [16] and antioxidant/anti-inflammatory activities [17, 18, 19], and also exerts preventive effects against osteoporosis and knee osteoarthritis [20]. We previously reported that \(\beta\)-cry exerted anti-inflammatory effects in periodontal ligament-derived cells [21]. We recently showed that \(\beta\)-cry exerted anti-inflammatory effects against the inflammatory responses of epithelial cells induced by 5-FU, a chemotherapeutic agent [22]. However, it currently remains unclear whether \(\beta\)-cry attenuates oral mucositis, which occurs as a side effect of CDDP, an anticancer drug that is frequently used to treat head and neck cancers. Furthermore, the oral mucosa consists of not only an epithelial layer, but also a connective tissue layer, and oral mucositis is induced in both layers. Moreover, the effects of \(\beta\)-cry on oral mucosal fibroblasts have yet to be clarified. Therefore, we herein examined the effects of CDDP and \(\beta\)-cry individually and in combination on oral mucosa-derived cells (keratinocytes and fibroblasts).