Evaluating the potential bioactivity of a novel compound ER1626.
BACKGROUND
ER1626, a novel compound, is a derivate of indeno-isoquinoline ketone. This study was designed to evaluate the biological activity and potential anti-tumor mechanism of ER1626.


METHODS
MTT assay, scratch assay and flow cytometry were used to determine cell proliferation, cell migration and cell cycle distribution as well as cell apoptosis on human breast cancer MCF-7 cells and endometrial cancer Ishikawa cells. We also explored the antiangiogenic effect of ER1626 on HUVEC cells and chicken embryos. The expression of estrogen receptor protein was investigated with western-blot analysis.


RESULTS
ER1626 down-regulated the expression of estrogen receptor α protein and up-regulated β protein in MCF-7 and Ishikawa cells. The value of IC50 of ER1626 on MCF-7 and Ishikawa cells were respectively 8.52 and 3.08 µmol/L. Meanwhile, ER1626 decreased VEGF secretion of MCF-7 and Ishikawa cells, disturbed the formation of VEGF-stimulated tubular structure in HUVEC cells, and inhibited the angiogenesis on the chicken chorioallantoic membrane. Scratch assay revealed that ER1626 suppressed the migration of MCF-7, Ishikawa and HUVEC cells. In addition to induction tumor cell apoptosis, ER1626 arrested cell cycle in G1/G0 phase in MCF-7 cells and G2/M phase in Ishikawa cells.


CONCLUSIONS
In conclusion, our results demonstrated that ER1626 has favorable bioactivities to be a potential candidate against breast cancer and angiogenesis.
Nanjing Medical University, Affiliated Nanjing Brain Hospital, Nanjing, China.
Lijun
L
Wang
Nanjing Medical University, Affiliated Nanjing Brain Hospital, Nanjing, China.
Yanyan
Y
Zeng
Department of Pharmaceutical Chemistry, China Pharmaceutical University, Nanjing, China.
Tianling
T
Wang
Nanjing Medical University, Affiliated Nanjing Brain Hospital, Nanjing, China.
Hongyi
H
Liu
Nanjing Medical University, Affiliated Nanjing Brain Hospital, Nanjing, China.
Hong
H
Xiao
Department of Pharmaceutical Chemistry, China Pharmaceutical University, Nanjing, China.
Hua
H
Xiang
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D016889:Endometrial Neoplasms / Q000188:drug therapy*; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007192:Indenes / Q000737:chemistry / Q000494:pharmacology*; D007546:Isoquinolines / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D061986:MCF-7 Cells; D015394:Molecular Structure; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
C000592859:6-(4-(3-(diethylamino)propoxy)phenyl)-5H-indeno(1,2-c)isoquinoline-5,11(6H)-dione; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007192:Indenes; D007546:Isoquinolines; D007659:Ketones; D015363:Quinolones; D011960:Receptors, Estrogen; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue