OncoTargets and Therapy (Oct 2016)
The medicinal fungus Antrodia cinnamomea regulates DNA repair and enhances the radiosensitivity of human esophageal cancer cells
Abstract
Yu-Ming Liu,1–3,* Yu-Kuo Liu,4,* Ling-Wei Wang,1,3 Yu-Chuen Huang,5,6 Pin-I Huang,1,3 Tung-Hu Tsai,2 Yu-Jen Chen2,7 1Department of Oncology, Division of Radiation Oncology, Taipei Veterans General Hospital, 2School of Medicine, Institute of Traditional Medicine, National Yang Ming University, Taipei, 3School of Medicine, National Yang Ming University, Taipei, 4Department of Chemical and Material Engineering, Chang Gung University, Taoyuan City, 5Department of Medical Research, China Medical University Hospital, 6School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 7Department of Radiation Oncology, MacKay Memorial Hospital, New Taipei City, Taiwan *These authors contributed equally to this work Abstract: This study investigated the adjunctive effects of Antrodia cinnamomea mycelial fermentation broth (AC-MFB), a Taiwanese medicinal fungus, in enhancing the radiosensitivity of esophageal cancer cells. Human CE81T/VGH squamous and BE3 adenocarcinoma esophageal cancer cells were used in this study. A colony formation assay showed that pretreatment with AC-MFB decreased the survival of irradiated esophageal cancer cells, with a maximum sensitizer enhancement ratio of 1.91% and 37% survival. A DNA histogram study showed that AC-MFB pretreatment enhanced cell cycle arrest at the G2/M phase, the most radiosensitive phase. An immunofluorescence assay and a Western blotting assay showed that AC-MFB delayed the abrogation of γ-H2AX, upregulated p21 expression, and attenuated the radiation-induced phosphorylation of ataxia telangiectasia-mutated kinase and checkpoint kinase 2. An in vivo validation study showed that AC-MFB treatment tended to have a synergistic effect with radiation on the tumor growth delay of CE81T/VGH cells in BALB/c mice. These data suggest that this edible fungus product could enhance the effect of radiotherapy against esophageal cancer. Keywords: mycelial, G2/M, fermentation broth, radiosensitization, p21
