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Molecules 2017, 22(4), 629; doi:10.3390/molecules22040629

Metronomic Cordycepin Therapy Prolongs Survival of Oral Cancer-Bearing Mice and Inhibits Epithelial-Mesenchymal Transition

1
Division of Medical Oncology and Hematology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei 11094, Taiwan
2
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan
3
Department of Medical Research, Mackay Memorial Hospital, Taipei 25160, Taiwan
4
Department of Oral and Maxillofacial Surgery, Mackay Memorial Hospital, Taipei 11094, Taiwan
5
Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei 11221, Taiwan
6
Department of Chemical Engineering, National United University, Miaoli 36063, Taiwan
7
Department of Radiation Oncology, Mackay Memorial Hospital, Taipei 25160, Taiwan
8
Research Center for Chinese Medicine and Acupuncture, China Medical University, Taichung 404, Taiwan
*
Authors to whom correspondence should be addressed.
Academic Editor: Pinarosa Avato
Received: 14 February 2017 / Revised: 6 April 2017 / Accepted: 10 April 2017 / Published: 13 April 2017
View Full-Text   |   Download PDF [3486 KB, uploaded 13 April 2017]   |  

Abstract

Cordycepin (3′-deoxyadenosine) is a natural compound abundantly found in Cordyceps sinesis in natural and fermented sources. In this study, we examined the effects of cordycepin in a human oral squamous cell carcinoma (OSCC) xenograft model. Cordycepin was administered in a regular, low-dose and prolonged schedule metronomic therapy. Two doses of cordycepin (25 mg/kg, 50 mg/kg) were administrated five days a week for eight consecutive weeks. The tumor volumes were reduced and survival time was significantly prolonged from 30.3 ± 0.9 days (control group) to 56 days (50 mg/kg group, the day of tumor-bearing mice were sacrificed for welfare consideration). The weights of mice did not change and liver, renal, and hematologic functions were not compromised. Cordycepin inhibited the OSCC cell viability in vitro (IC50 122.4–125.2 μM). Furthermore, morphological characteristics of apoptosis, increased caspase-3 activity and G2/M cell cycle arrest were observed. In wound healing assay, cordycepin restrained the OSCC cell migration. Cordycepin upregulated E-cadherin and downregulated N-cadherin protein expression, implying inhibition of epithelial-mesenchymal transition (EMT). The immunohistochemical staining of xenograft tumor with E-cadherin and vimentin validated in vitro results. In conclusion, metronomic cordycepin therapy showed effective tumor control, prolonged survival and low toxicities. Cytotoxicity against cancer cells with apoptotic features and EMT inhibition were observed. View Full-Text
Keywords: cordycepin; epithelial-mesenchymal transition; oral squamous cell carcinoma metronomic therapy cordycepin; epithelial-mesenchymal transition; oral squamous cell carcinoma metronomic therapy
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Su, N.-W.; Wu, S.-H.; Chi, C.-W.; Liu, C.-J.; Tsai, T.-H.; Chen, Y.-J. Metronomic Cordycepin Therapy Prolongs Survival of Oral Cancer-Bearing Mice and Inhibits Epithelial-Mesenchymal Transition. Molecules 2017, 22, 629.

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