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

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.

• Authors: Nai-Wen Su, Shu-Hua Wu, Chih-Wen Chi, Chung-Ji Liu, Tung-Hu Tsai, Yu-Jen Chen
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 22 Issue 4 (Apr 13 2017) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 28406456 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Deoxyadenosines
• cordycepin

Topics

• Administration, Metronomic
• Animals
• Antineoplastic Agents (administration & dosage, chemistry)
• Apoptosis (drug effects)
• Carcinoma, Squamous Cell
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Deoxyadenosines (administration & dosage, chemistry)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Epithelial-Mesenchymal Transition (drug effects)
• Humans
• Mice
• Molecular Structure
• Mouth Neoplasms (drug therapy, mortality, pathology)
• Tumor Burden (drug effects)
• Wound Healing (drug effects)
• Xenograft Model Antitumor Assays