PMID- 20664987
OWN - NLM
STAT- MEDLINE
DCOM- 20101123
LR  - 20211203
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 24
IP  - 3
DP  - 2010 Sep
TI  - In vitro mechanism of action for the cytotoxicity elicited by the combination of 
      epigallocatechin gallate and raloxifene in MDA-MB-231 cells.
PG  - 779-85
AB  - The anticancer effects elicited by epigallocatechin gallate (EGCG) are well 
      established in various models of cancer, while raloxifene is as an established 
      selective estrogen receptor modulator (SERM), which is not yet clinically 
      utilized for the treatment of breast cancer. Previous study from this laboratory 
      has demonstrated that the combination of EGCG (25 microM) and raloxifene (4 
      microM) elicits a strong cytotoxic response in MDA-MB-231 human breast cancer 
      cells, which lack the estrogen receptor (ER) and erbB-2/ Her-2 receptor. This 
      study was therefore designed to probe the mechanism underlying this cytotoxic 
      response, with an emphasis on determining how the combination treatment 
      influenced the total expression and phosphorylation of key signaling proteins. 
      Specifically, following 12 and 18 h of the combination treatment, we observed 
      significant decreases in the phosphorylation of the epidermal growth factor 
      receptor (EGFR), AKT, mammalian target of rapamycin (mTOR) and S-6-kinase (S6K), 
      and significant increases in the phosphorylation of stress activated protein 
      kinases (SAPKs). Furthermore, these changes were associated with a reduction in 
      the nuclear localization of p65, a major subunit of NF-kappaB. These results 
      demonstrate that the combination of EGCG and raloxifene effectively reduced the 
      mitogenic and survival signaling in MDA-MB-231 cells. Thus, this combination 
      warrants further experimentation as a potential treatment for ER-negative breast 
      cancer.
FAU - Stuart, Emma C
AU  - Stuart EC
AD  - Department of Pharmacology and Toxicology, University of Otago, Dunedin, New 
      Zealand.
FAU - Jarvis, Reagan M
AU  - Jarvis RM
FAU - Rosengren, Rhonda J
AU  - Rosengren RJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (RELA protein, human)
RN  - 0 (Selective Estrogen Receptor Modulators)
RN  - 0 (Transcription Factor RelA)
RN  - 4F86W47BR6 (Raloxifene Hydrochloride)
RN  - 8R1V1STN48 (Catechin)
RN  - BQM438CTEL (epigallocatechin gallate)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology
MH  - Breast Neoplasms/*metabolism/pathology
MH  - Catechin/analogs & derivatives/pharmacology
MH  - Cell Line, Tumor
MH  - ErbB Receptors/metabolism
MH  - Estrogen Receptor alpha/deficiency
MH  - Female
MH  - Humans
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Raloxifene Hydrochloride/pharmacology
MH  - Receptor, ErbB-2/deficiency
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - Selective Estrogen Receptor Modulators/pharmacology
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Time Factors
MH  - Transcription Factor RelA/metabolism
EDAT- 2010/07/29 06:00
MHDA- 2010/12/14 06:00
CRDT- 2010/07/29 06:00
PHST- 2010/07/29 06:00 [entrez]
PHST- 2010/07/29 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - 10.3892/or_00000921 [doi]
PST - ppublish
SO  - Oncol Rep. 2010 Sep;24(3):779-85. doi: 10.3892/or_00000921.