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

Hitoshi Yoshimura, Hisato Yoshida, Shinpei Matsuda, Takashi Ryoke, Keiichi Ohta, Masahiro Ohmori, Satoshi Yamamoto, Tamotsu Kiyoshima, Motohiro Kobayashi, Kazuo Sano

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1139-1148
Number of pages10
JournalMolecular medicine reports
Volume20
Issue number2
DOIs
Publication statusPublished - Jan 1 2019

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Cell proliferation
Heterografts
Squamous Cell Carcinoma
Cell Proliferation
Apoptosis
Cells
Therapeutics
Staining and Labeling
Caspase 7
Tumors
Caspase 3
Labeling
Control Groups
Neoplasms
Cell Cycle
epigallocatechin gallate
In Vitro Techniques
Epithelial Cells
Propidium
Annexin A5

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

Cite this

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. / Yoshimura, Hitoshi; Yoshida, Hisato; Matsuda, Shinpei; Ryoke, Takashi; Ohta, Keiichi; Ohmori, Masahiro; Yamamoto, Satoshi; Kiyoshima, Tamotsu; Kobayashi, Motohiro; Sano, Kazuo.

In: Molecular medicine reports, Vol. 20, No. 2, 01.01.2019, p. 1139-1148.

Research output: Contribution to journalArticle

Yoshimura, Hitoshi ; Yoshida, Hisato ; Matsuda, Shinpei ; Ryoke, Takashi ; Ohta, Keiichi ; Ohmori, Masahiro ; Yamamoto, Satoshi ; Kiyoshima, Tamotsu ; Kobayashi, Motohiro ; Sano, Kazuo. / 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. In: Molecular medicine reports. 2019 ; Vol. 20, No. 2. pp. 1139-1148.
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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.",
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