MCI-186 inhibits tumor growth through suppression of EGFR phosphorylation and cell cycle arrest.
BACKGROUND
It has been suggested that radicals stimulate tumor cell growth. We examined if the hydroxyl radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), affects tumor growth in vitro.


METHODS
Human hepatocarcinoma HepG2, mesothelioma MSTO-211H, gastric carcinoma TMK-1 and breast carcinoma MCF-7 were used for cell proliferation assay. Cell cycle analysis was performed using propidium iodide for fluorescence activated cell sorter. By Western blotting, EGF receptor (EGFR) phosphorylation and EGFR expression were analyzed.


RESULTS
Growth inhibition was observed from 10 microM to 300 microM of MCI-186 in a dose-dependent manner. Cell cycle analysis revealed that MCI-186 arrested the cell cycle at the G0/G1-phase. MCI-186 inhibited EGF-stimulated cell growth. The phosphorylation level of EGFR was decreased by MCI-186, but the EGFR level was unchanged.


CONCLUSIONS
From the data obtained, we suggest that tumor inhibition by MCI-186 was due, at least in part, to the modulation of EGFR signaling and cell cycle arrest.
Suzuki
Ryoko
R
Department of Thoracic and Cardiovascular Surgery and Regeneration Technology, Faculty of Medicine, Kochi University, Kochi, Japan.
Gopalrao
Rajesh Katare
RK
Maeda
Hironori
H
Rao
Parijatha
P
Yamamoto
Morio
M
Xing
Yutong
Y
Mizobuchi
Shunji
S
Sasaguri
Shiro
S
D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D000077553:Edaravone; D066246:ErbB Receptors / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D016192:Resting Phase, Cell Cycle / Q000187:drug effects
D000970:Antineoplastic Agents; D000975:Antioxidants; D016166:Free Radical Scavengers; D066246:ErbB Receptors; D000077553:Edaravone; D000983:Antipyrine