[SUCI02 inhibits HER-2/neu receptor tyrosine kinase phosphorylation and growth of HER-2/neu-overexpressing breast cancer cells].
OBJECTIVE
Overexpression of HER-2/neu receptor plays a key role in tumorigenesis,progression,prognosis and chemosensitivity of tumors. We found that SUCI02[N-(4-ethoyphenol)-2-hydroxy- acid amide] could inhibit HER2/neu phosphorylation through comprehensive screening. The aim of this study was to examine the effect of SUCI02 on HER-2/neu-overexpressing cancer cell growth.


METHODS
Western blot analysis and immunoprecipitation was used to examine the changes of HER-2/neu receptor tyrosine kinase phosphorylation and protein level. MTT assay was employed to determine the growth inhibition of SUCI02 on the tumor cells.


RESULTS
SUCI02 reversibly inhibited tyrosine phosphorylation of HER-2/neu in a dose-dependent manner with half maximal inhibition at a concentration of 4.34 microg/ml without reduced HER-2/neu receptor protein expression. Activation of MAPK and AKT, which were downstream molecules of HER-2/neu-mediated signal transduction pathway, was inhibited after being exposure to SUCI02. In contrast, tyrosine phosphorylation of EGFR was relatively unaffected at the concentrations of SUCI02 up to 40 microg/ml. SUCI02 inhibited cell proliferation of HER-2/neu- overexpressing MDA-MB-453m1 more potent than that of EGFR-overexpressing MDA-MB-468.Their IC(50) values were 1.33 microg/ml and 11.3 microg/ml,respectively.


CONCLUSIONS
SUCI02 can inhibit tyrosine phosphorylation of HER-2/neu receptor,cell proliferation of HER-2/neu-overexpressing breast cancer cells preferentially and shut down downstream HER-2/neu signal transduction.
Zhu
Xiao-Feng
XF
Cancer Institute,Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, PR China. xfzhu70@public.guangzhou.gd.cn
Liu
Zong-Chao
ZC
Xie
Bing-Fen
BF
Cai
Li-Ling
LL
Yang
Da-Jun
DJ
D000577:Amides / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D006880:Hydroxy Acids / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D000577:Amides; D000970:Antineoplastic Agents; D006880:Hydroxy Acids; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D014443:Tyrosine; C480138:N-(4-ethoyphenol)-2-hydroxy- acid amide; C494918:AKT1 protein, human