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Combination of CYP inhibitor with MEK/ERK inhibitor enhances the inhibitory effect on ERK in BRAF mutant colon cancer cells.

Authors
 SUN MIN LIM  ;  JEE WON HWANG  ;  JOONG BAE AHN  ;  SOO KYUNG BAE  ;  CHAN HEE PARK  ;  KI-YEOL KIM  ;  SUN YOUNG RHA  ;  HYUN CHEOL CHUNG  ;  JAE KYUNG ROH  ;  SANG JOON SHIN 
Citation
 Anticancer Research, Vol.33(6) : 2499-2508, 2013 
Journal Title
 Anticancer Research 
ISSN
 0250-7005 
Issue Date
2013
MeSH
Benzoflavones/pharmacology ; Butadienes/pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Colonic Neoplasms/drug therapy* ; Colonic Neoplasms/genetics ; Cytochrome P-450 CYP1A1/antagonists & inhibitors* ; Cytochrome P-450 CYP1A1/metabolism ; Cytochrome P-450 CYP1A2/metabolism ; Enzyme Inhibitors/pharmacology ; Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors* ; Humans ; MAP Kinase Signaling System/drug effects ; Nitriles/pharmacology ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors*
Keywords
CYP inhibitor ; Cell signaling ; ERK ; HCT116 ; HT29 ; MEK/ERK inhibitor ; U0126 ; colorectal cancer
Abstract
BACKGROUND/AIM: To investigate mechanisms of discrepancy in response to a MEK/ERK inhibitor, U0126, in KRAS- and BRAF-mutant colorectal cancer cells. MATERIALS AND METHODS: Multiparametric flow cytometry was performed on two colon cancer cell lines, HCT116 and HT29. Cells were treated with U0126, and phospho-specific antibodies were used to monitor ERK signaling. RESULTS: HCT116 and HT29 cells were treated with increasing amounts of U0126. The western blot analysis revealed that by increasing the amount of U0126 resulted in inhibition of phospho-ERK, in HCT116 and to a lesser degree in HT29 cells. Microarray profiling identified CYP1A1 and 1A2 overexpression in HT29 cells and that inhibition of CYP1A1 with α-naphthoflavone and furanfylline restored sensitivity to U0126 in HT29 cells. CONCLUSION: Combination of a CYP inhibitor with MEK/ERK inhibitor enhances the inhibitory effect on ERK in BRAF-mutant colon cancer cells.
Full Text
http://ar.iiarjournals.org/content/33/6/2499.long
DOI
23749901
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Ki Yeol(김기열) ORCID logo https://orcid.org/0000-0001-5357-1067
Roh, Jae Kyung(노재경)
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Park, Chan Hee(박찬희)
Shin, Sang Joon(신상준) ORCID logo https://orcid.org/0000-0001-5350-7241
Ahn, Joong Bae(안중배) ORCID logo https://orcid.org/0000-0001-6787-1503
Lim, Sun Min(임선민)
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/87808
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