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

• Published in: Molecular medicine reports Vol. 20; no. 2; pp. 1139 - 1148
• Main Authors: Yoshimura, Hitoshi, Yoshida, Hisato, Matsuda, Shinpei, Ryoke, Takashi, Ohta, Keiichi, Ohmori, Masahiro, Yamamoto, Satoshi, Kiyoshima, Tamotsu, Kobayashi, Motohiro, Sano, Kazuo
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.08.2019; Spandidos Publications UK Ltd; D.A. Spandidos
• Subjects: Analysis; Animal experimentation; Animal models; Animals; Annexin V; Apoptosis; Apoptosis - drug effects; Biotechnology industries; Cancer; Cancer cells; Cancer research; Cancer therapies; Carcinoma; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - physiopathology; Caspase; Caspase-3; Catechin; Catechin - analogs & derivatives; Catechin - pharmacology; Catechin - therapeutic use; Cell cycle; Cell growth; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Cell viability; DNA nucleotidylexotransferase; DNA polymerases; Epigallocatechin-3-gallate; Female; G1 phase; Green tea; Health aspects; Humans; Kinases; Mice; Mice, Inbred BALB C; Mice, Nude; Mouth Neoplasms - drug therapy; Mouth Neoplasms - physiopathology; Oral cancer; Oral squamous cell carcinoma; Propidium iodide; Squamous cell carcinoma; Tea; Tea (Beverage); Therapeutic applications; Tumor cells; Tumors; Xenograft Model Antitumor Assays; Xenografts; Japan
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2019.10331

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.