PMID- 31173211 OWN - NLM STAT- MEDLINE DCOM- 20191230 LR - 20200225 IS - 1791-3004 (Electronic) IS - 1791-2997 (Print) IS - 1791-2997 (Linking) VI - 20 IP - 2 DP - 2019 Aug TI - 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. PG - 1139-1148 LID - 10.3892/mmr.2019.10331 [doi] AB - 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. FAU - Yoshimura, Hitoshi AU - Yoshimura H AD - Department of Dentistry and Oral Surgery, Unit of Sensory and Locomotor Medicine, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui 910‑1193, Japan. FAU - Yoshida, Hisato AU - Yoshida H AD - Department of Dentistry and Oral Surgery, Unit of Sensory and Locomotor Medicine, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui 910‑1193, Japan. FAU - Matsuda, Shinpei AU - Matsuda S AD - Department of Dentistry and Oral Surgery, Unit of Sensory and Locomotor Medicine, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui 910‑1193, Japan. FAU - Ryoke, Takashi AU - Ryoke T AD - Department of Dentistry and Oral Surgery, Unit of Sensory and Locomotor Medicine, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui 910‑1193, Japan. FAU - Ohta, Keiichi AU - Ohta K AD - Department of Dentistry and Oral Surgery, Unit of Sensory and Locomotor Medicine, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui 910‑1193, Japan. FAU - Ohmori, Masahiro AU - Ohmori M AD - Department of Dentistry and Oral Surgery, Unit of Sensory and Locomotor Medicine, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui 910‑1193, Japan. FAU - Yamamoto, Satoshi AU - Yamamoto S AD - Department of Dentistry and Oral Surgery, Unit of Sensory and Locomotor Medicine, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui 910‑1193, Japan. FAU - Kiyoshima, Tamotsu AU - Kiyoshima T AD - Laboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Fukuoka 812‑8582, Japan. FAU - Kobayashi, Motohiro AU - Kobayashi M AD - Department of Tumor Pathology, Unit of Pathological Sciences, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui 910‑1193, Japan. FAU - Sano, Kazuo AU - Sano K AD - Department of Dentistry and Oral Surgery, Unit of Sensory and Locomotor Medicine, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui 910‑1193, Japan. LA - eng PT - Journal Article DEP - 20190604 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 8R1V1STN48 (Catechin) RN - BQM438CTEL (epigallocatechin gallate) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Carcinoma, Squamous Cell/*drug therapy/physiopathology MH - Catechin/*analogs & derivatives/pharmacology/therapeutic use MH - Cell Line, Tumor MH - Cell Proliferation/*drug effects MH - Female MH - Humans MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Mouth Neoplasms/*drug therapy/physiopathology MH - Xenograft Model Antitumor Assays PMC - PMC6625387 EDAT- 2019/06/08 06:00 MHDA- 2019/12/31 06:00 PMCR- 2019/06/04 CRDT- 2019/06/08 06:00 PHST- 2018/10/19 00:00 [received] PHST- 2019/05/10 00:00 [accepted] PHST- 2019/06/08 06:00 [pubmed] PHST- 2019/12/31 06:00 [medline] PHST- 2019/06/08 06:00 [entrez] PHST- 2019/06/04 00:00 [pmc-release] AID - mmr-20-02-1139 [pii] AID - 10.3892/mmr.2019.10331 [doi] PST - ppublish SO - Mol Med Rep. 2019 Aug;20(2):1139-1148. doi: 10.3892/mmr.2019.10331. Epub 2019 Jun 4.