Abstract
PurposeRadiation-induced oral mucositis limits the delivery of high-dose radiation to head and neck cancer. This study investigated the effectiveness of epicatechin (EC), a component of green tea extracts, on radiation-induced oral mucositis in vitro and in vivo.Experimental DesignThe effect of EC on radiation-induced cytotoxicity was analyzed in the human keratinocyte line HaCaT. Radiation-induced apoptosis, change in mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation and changes in the signaling pathway were investigated. In vivo therapeutic effects of EC for oral mucositis were explored in a rat model. Rats were monitored by daily inspections of the oral cavity, amount of oral intake, weight change and survival rate. For histopathologic evaluation, hematoxylin-eosin staining and TUNEL staining were performed.ResultsEC significantly inhibited radiation-induced apoptosis, change of MMP, and intracellular ROS generation in HaCaT cells. EC treatment markedly attenuated the expression of p-JNK, p-38, and cleaved caspase-3 after irradiation in the HaCaT cells. Rats with radiation-induced oral mucositis showed decreased oral intake, weight and survival rate, but oral administration of EC significantly restored all three parameters. Histopathologic changes were significantly decreased in the EC-treated irradiated rats. TUNEL staining of rat oral mucosa revealed that EC treatment significantly decreased radiation-induced apoptotic cells.ConclusionsThis study suggests that EC significantly inhibited radiation-induced apoptosis in keratinocytes and rat oral mucosa and may be a safe and effective candidate treatment for the prevention of radiation-induced mucositis.
Highlights
Radiotherapy has become increasingly important for the treatment of head and neck squamous cell carcinoma [1,2]
This study suggests that EC significantly inhibited radiation-induced apoptosis in keratinocytes and rat oral mucosa and may be a safe and effective candidate treatment for the prevention of radiation-induced mucositis
Oral mucositis may significantly detract from the quality of life of cancer patients undergoing radiotherapy or chemotherapy
Summary
Radiotherapy has become increasingly important for the treatment of head and neck squamous cell carcinoma [1,2]. Oral mucositis, associated with both radiation and chemotherapy, is a very common, painful, and dose-limiting toxicity, with an incidence that can be as high as 90% [3]. Radiation-induced oral mucositis may be accompanied by altered taste, pain, dry mouth, decreased appetite, and even ulceration, and can lead to decreased nutritional uptake [3,4]. The presence of ulcerative oral mucositis in granulocytopenic patients often leads to systemic infections, and even to fatal consequences. Oral mucositis may significantly detract from the quality of life of cancer patients undergoing radiotherapy or chemotherapy. Oral mucositis can cause clinicians to interrupt the therapy of patients, which is quite undesirable as it can limit the success of therapy. There have been a lot of efforts to mitigate radiation-induced oral mucositis. [6] [7] [8] [9] [10] [11] [12] [13,14] [3,15] Despite this, no intervention has yet been completely successful in preventing radiation-induced oral mucositis [16]
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