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Food Chem Toxicol. 2019 Feb;124:400-410. doi: 10.1016/j.fct.2018.12.025. Epub 2018 Dec 18.

Cordycepin, isolated from medicinal fungus Cordyceps sinensis, enhances radiosensitivity of oral cancer associated with modulation of DNA damage repair.

Author information

1
Division of Medical Oncology and Hematology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, 11094, Taiwan; Institute of Tradition Medicine, School of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan.
2
Department of Medical Research, MacKay Memorial Hospital, Taipei, 25160, Taiwan.
3
Institute of Tradition Medicine, School of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan; Department of Chemical Engineering, National United University, Miaoli, 36063, Taiwan. Electronic address: thtsai@ym.edu.tw.
4
Institute of Tradition Medicine, School of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan; Department of Medical Research, MacKay Memorial Hospital, Taipei, 25160, Taiwan; Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, 25160, Taiwan; Research Center for Chinese Medicine and Acupuncture, China Medical University, Taichung, 40402, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, 40402, Taiwan. Electronic address: chenmdphd@gmail.com.

Abstract

Concurrent chemotherapy and radiotherapy (RT) is important for controlling oral squamous cell carcinoma (OSCC), which is often accompanied by significant acute and late toxicities. We investigated whether cordycepin, a small molecule extracted from Cordyceps sinensis, could enhance the radiosensitivity of oral cancer cells. Using colony formation assay, we demonstrated that cordycepin induces radiosensitizing effects on two OSCC cells. DNA histogram analysis showed that cordycepin combined with RT prolonged the RT-induced G2/M phase arrest. It protracted the duration of DNA double strand breaks, which was detected by immunofluorescent staining of phosphorylated histone H2AX (γ-H2AX). The underlying molecular mechanism might involve the downregulation of protein expression related to DNA damage repair, including phosphorylated ataxia-telangiectasia mutated (p-ATM) and phosphorylated checkpoint kinase 2. Reciprocal upregulation of phosphorylated checkpoint kinase 1 (Chk1) expression was noted, and the radiosensitizing effect of cordycepin could be further augmented by Chk1 mRNA knockdown, indicating a compensatory DNA repair machinery involving phosphorylation of Chk1. In vivo, the combination of cordycepin and RT exhibited greater growth inhibition on xenografts and stronger apoptosis induction than RT alone, without exacerbating major toxicities. In conclusion, cordycepin increased the radiosensitivity of OSCC cells, which is associated with the modulation of RT-induced DNA damage repair machinery.

KEYWORDS:

Cordycepin; DNA damage response; Oral squamous cell carcinoma; Radiosensitivity; Radiotherapy

PMID:
30576710
DOI:
10.1016/j.fct.2018.12.025
[Indexed for MEDLINE]

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