PMID- 27200496
OWN - NLM
STAT- MEDLINE
DCOM- 20170406
LR  - 20211025
IS  - 1522-7278 (Electronic)
IS  - 1520-4081 (Linking)
VI  - 32
IP  - 3
DP  - 2017 Mar
TI  - Epigallocatechin gallate sensitizes cisplatin-resistant oral cancer CAR cell 
      apoptosis and autophagy through stimulating AKT/STAT3 pathway and suppressing 
      multidrug resistance 1 signaling.
PG  - 845-855
LID - 10.1002/tox.22284 [doi]
AB  - Epigallocatechin gallate (EGCG) is a green tea polyphenol that presents 
      anticancer activities in multiple cancer cells, but no available report was 
      addressed for the underling molecular mechanism of cytotoxic impacts on 
      drug-resistant oral squamous cell carcinoma cells. In the present study, the 
      inhibitory effects of EGCG were experienced on cisplatin-resistant oral cancer 
      CAR cells. EGCG inhibited cell viability in a time- and concentration-dependent 
      manner by a sulforhodamine B (SRB) assay. EGCG induced CAR cell apoptosis and 
      autophagy by 4',6-diamidino-2-phenylindole (DAPI) dye, acridine orange (AO) 
      staining and green fluorescent protein (GFP)-tagged LC3B assay, respectively. 
      EGCG also significantly enhanced caspase-9 and caspase-3 activities by caspase 
      activity assay. EGCG markedly increased the protein levels of Bax, cleaved 
      caspase-9, cleaved caspase-3, Atg5, Atg7, Atg12, Beclin-1, and LC3B-II, as well 
      as significantly decreased the expression of Bcl-2, phosphorylated AKT (Ser473) 
      and phosphorylation of STAT3 on Tyr705 by western blotting in CAR cells. 
      Importantly, the protein and gene expression of multidrug resistance 1 (MDR1) 
      were dose-dependently inhibited by EGCG. Overall, downregulation of MDR1 levels 
      and alterations of AKT/STAT3 signaling contributed to EGCG-induced apoptosis and 
      autophagy in CAR cells. Based on these results, EGCG has the potential for 
      therapeutic effect on oral cancer and may be useful for long-term oral cancer 
      prevention in the future. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 
      845-855, 2017.
CI  - (c) 2016 Wiley Periodicals, Inc.
FAU - Yuan, Chien-Han
AU  - Yuan CH
AD  - Department of Otolaryngology, Kaohsiung Armed Forces General Hospital, Kaohsiung, 
      Taiwan.
AD  - Department of Otorhinolaryngology Head and Neck Surgery, Tri-Service General 
      Hospital, National Defense Medical Center, Taipei, Taiwan.
FAU - Horng, Chi-Ting
AU  - Horng CT
AD  - Kaohsiung Armed Forces General Hospital, Medical Education Center, Kaohsiung, 
      Taiwan.
AD  - Institute of Biochemistry and Biotechnology, Chung Shan Medical University and 
      Chung Shan Medical University Hospital, Taichung, Taiwan.
FAU - Lee, Chiu-Fang
AU  - Lee CF
AD  - Kaohsiung Veterans General Hospital Pingtung Branch, Pingtung, Taiwan.
FAU - Chiang, Ni-Na
AU  - Chiang NN
AD  - Kaohsiung Veterans General Hospital Pingtung Branch, Pingtung, Taiwan.
FAU - Tsai, Fuu-Jen
AU  - Tsai FJ
AD  - Human Genetic Center, China Medical University Hospital, Taichung, Taiwan.
AD  - School of Post-Baccalaureate Chinese Medicine, China Medical University, 
      Taichung, Taiwan.
FAU - Lu, Chi-Cheng
AU  - Lu CC
AD  - School of Nutrition and Health Sciences, Taipei Medical University, Taipei, 
      Taiwan.
FAU - Chiang, Jo-Hua
AU  - Chiang JH
AD  - Department of Nursing, Chung-Jen Junior College of Nursing, Health Sciences and 
      Management, Chiayi County, Taiwan.
FAU - Hsu, Yuan-Man
AU  - Hsu YM
AD  - Department of Biological Science and Technology, China Medical University, 
      Taichung, Taiwan.
FAU - Yang, Jai-Sing
AU  - Yang JS
AD  - Department of Medical Research, China Medical University Hospital, China Medical 
      University, Taichung, Taiwan.
FAU - Chen, Fu-An
AU  - Chen FA
AD  - Department of Pharmacy and Master Program, Tajen University, Pingtung, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20160520
PL  - United States
TA  - Environ Toxicol
JT  - Environmental toxicology
JID - 100885357
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Autophagy-Related Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 8R1V1STN48 (Catechin)
RN  - BQM438CTEL (epigallocatechin gallate)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 9)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics/metabolism
MH  - Apoptosis/*drug effects
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Autophagy/*drug effects
MH  - Autophagy-Related Proteins/metabolism
MH  - Caspase 3/metabolism
MH  - Caspase 9/metabolism
MH  - Catechin/*analogs & derivatives/pharmacology
MH  - Cell Line, Tumor
MH  - Cisplatin/pharmacology/*toxicity
MH  - Down-Regulation/drug effects
MH  - Humans
MH  - Microscopy, Fluorescence
MH  - Mouth Neoplasms/metabolism/pathology
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Signal Transduction/*drug effects
OTO - NOTNLM
OT  - AKT/STAT3 signaling
OT  - MDR1
OT  - apoptosis
OT  - autophagy
OT  - epigallocatechin gallate
EDAT- 2016/05/21 06:00
MHDA- 2017/04/07 06:00
CRDT- 2016/05/21 06:00
PHST- 2016/03/31 00:00 [received]
PHST- 2016/04/21 00:00 [revised]
PHST- 2016/04/30 00:00 [accepted]
PHST- 2016/05/21 06:00 [pubmed]
PHST- 2017/04/07 06:00 [medline]
PHST- 2016/05/21 06:00 [entrez]
AID - 10.1002/tox.22284 [doi]
PST - ppublish
SO  - Environ Toxicol. 2017 Mar;32(3):845-855. doi: 10.1002/tox.22284. Epub 2016 May 
      20.