Cordycepin Enhances Radiosensitivity in Oral Squamous Carcinoma Cells by Inducing Autophagy and Apoptosis Through Cell Cycle Arrest.

Ho Ho,Chiu Chiu,Huang Huang,Lin Lin,Yeh Yeh,Wu Wu,Wang Wang

doi:10.3390/ijms20215366

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide and accounts for over 90% of malignant neoplasms of the oral cavity, with a 5-year survival rate of less than 50%. The long-term survival rate of OSCC patients has not markedly improved in recent decades due to its heterogeneous etiology and treatment outcomes. We investigated the anticancer effect of the combination of irradiation (IR) and cordycepin in the treatment of human OSCC cells in vitro. The type of cell death, especially autophagy and apoptosis, and the underlying mechanisms were examined. We found synergistic effects of cordycepin and IR on the viability of human oral cancer cells. The combination of cordycepin and IR treatment induced apoptosis, cell cycle arrest, and autophagic cell death. Furthermore, cordycepin induced S-phase arrest and prolonged G2/M arrest in the cells that received the combination treatment compared with those that received irradiation alone. Combined treatment induced the upregulation of ATG5 and p21 in an autophagy cascade-dependent manner, arrested the cell cycle in the G2/M phase, and repressed cell proliferation. Thus, we conclude that the combination of cordycepin and IR treatment could be a potential therapeutic strategy for OSCC.

Highlights

Oral squamous cell carcinoma (OSCC), a major subtype of head and neck carcinoma displaying many pathological differences from cancers found at other sites in the head and neck region, is among the top 12 most common cancers worldwide [1,2]
The results show that cell viability among the three cell lines significantly decreased by increasing the dosage of cordycepin alone or IR alone (p < 0.05) (Figure 1a,b)
The results show that increasing the doses of IR (2, 4, 6, and 8 Gy) and cordycepin (25, 50, 100, and 200 μM) for 48 and 72 h significantly reduced SAS cell viability (Figure 1d,e) (p < 0.05)

Summary

Introduction

Oral squamous cell carcinoma (OSCC), a major subtype of head and neck carcinoma displaying many pathological differences from cancers found at other sites in the head and neck region, is among the top 12 most common cancers worldwide [1,2]. OSCC accounts for over 90% of malignant neoplasms of the oral cavity, with a 5-year survival rate of less than 50% [3]. Exposure to multiple carcinogenic factors, including tobacco and alcohol, the most dominant etiologic factors of OSCC, has been identified to critically contribute to this malignancy [4]. Within the context of CRT, the optimal dose for OSCC irradiation (IR) is not clearly defined. To diminish the damage to normal tissue, treatment with chemical modifiers as radiosensitizers in combination with lower dose irradiation may augment overall therapeutic efficacy [5,6]

Objectives

Methods

Results

Conclusion