The therapeutic potential of epigallocatechin‑3‑gallate against human oral squamous cell carcinoma through inhibition of cell proliferation and induction of apoptosis: In�vitro and in�vivo murine xenograft study

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the oral region. Despite current therapeutic strategies, the survival rate has not been improved for several decades. Thus, it is important to develop a novel approach for the treatment of OSCC. Epigallocatechin-3-gallate (EGCG) is a major constituent of green tea and has previously been demonstrated to inhibit the growth of several types of cancer cells. However, few studies have investigated the effect of EGCG on human OSCC cells, especially in experimental animal models. The aim of the present study was to evaluate the therapeutic potential of EGCG for targeting human OSCC in vitro and in vivo . In the in vitro experiments, EGCG suppressed HSC-3 cell viability in a time- and dose-dependent manner. Cell cycle analysis revealed that EGCG induced G1 phase arrest of the tumor cells. Apoptosis was examined by Annexin V and propidium iodide staining, assays of caspase-3 and −7 activity and TdT-mediated dUTP nick end labeling (TUNEL) staining. Treatment with EGCG significantly increased caspase-3 and −7 activities, and the percentage of apoptotic cells when compared with control cells. In the in vivo xenograft experiment on mice, EGCG treatment resulted in a 45.2% reduction in tumor size as compared with the control group without weight loss. In vivo cell proliferation and apoptosis were assessed by immunohistochemical Ki-67 staining and the TUNEL staining. There were significant differences in Ki-67 expression between the EGCG treatment group and control group, and the percentage of apoptotic cells in the EGCG treatment group was significantly greater than that in the control group. These results indicated that EGCG significantly inhibited cell proliferation by affecting the cell cycle progression and apoptosis in vitro and in vivo . These findings suggest that EGCG may have clinical applications as a novel approach to oral-cancer therapy.

Wine Consumption and Oral Cavity Cancer: Friend or Foe, Two Faces of Janus

“…Oral and head and neck cancer cells exposed to green tea and epigallocatechin-3-gallate (EGCG), respectively, lead to a decrease in the expression of the phosphorylated epidermal growth factor receptor (EGFR), suggesting that catechins are potential cancer chemo-therapeutic or chemo-preventive agents [77,78]. In vitro, tea catechins promote a decrease in the proliferation of different human head and neck squamous cell carcinoma (HNSCC) cell lines [77][78][79][80][81][82]. Li et al [82] found that EGCG affects the proliferation, apoptosis, migration and invasion of tongue squamous cell carcinoma cells through the Hippo-TAZ signaling pathway.…”

“…Moreover, polyphenols alone induce G0/G1 cell-cycle arrest and apoptosis [83]. EGCG also induces the G1 phase arrest of human OSCC cells [81]. Activation of the p53 tumor suppressor gene by green tea polyphenols could explain the induction of cell cycle arrest and apoptosis [84].…”

“…Activation of the p53 tumor suppressor gene by green tea polyphenols could explain the induction of cell cycle arrest and apoptosis [84]. Treatment with EGCG increases caspase-3 and -7 activities and the percentage of apoptotic cells [81]. In addition, it was observed that EGCG induces cell apoptosis and autophagy and inhibits multi-drug resistance gene (MDR1) expression in oral cancer cells [85].…”

UBE2C is a Potential Biomarker for Tumorigenesis and Prognosis in Tongue Squamous Cell Carcinoma

“…OSCC is a highly aggressive cancer with frequent local recurrences and lymph node metastases [4]. The overall 5-year survival rate for OSCC patients have not been improved and remained at approximately 50% for several decades [5]. Therefore, how a diagnostic/prognostic assessment of gene expression could be translated into better patient survival.…”

The Potential of Phytochemicals in Oral Cancer Prevention and Therapy: A Review of the Evidence

“…Clinical trials have also shown that drinking more than 10 cups of green tea per day reduces the risk and delays the onset of cancer compared to those who drink less than 3 cups per day. In addition, smokers taking green tea extract (2000-2500 mg/day) for 4 weeks reduced the DNA damage of oral keratinocytes [217,218].…”