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Antiangiogenic 1‐Aryl‐3‐[3‐(thieno[3,2‐ b ]pyridin‐7‐ylthio)phenyl]ureas Inhibit MCF‐7 and MDA‐MB‐231 Human Breast Cancer Cell Lines Through PI3K/Akt and MAPK/Erk Pathways
Author(s) -
Machado Vera A.,
Peixoto Daniela,
Queiroz Maria João,
Soares Raquel
Publication year - 2016
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25580
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , breast cancer , cancer research , apoptosis , cancer , mapk/erk pathway , cytotoxicity , mcf 7 , cancer cell , cell growth , chemistry , mtt assay , medicine , human breast , biochemistry , signal transduction , in vitro
Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer related deaths among women worldwide. The purpose of this study is to evaluate the cytotoxic effects and possible molecular mechanisms of the antiproliferative properties of the antiangiogenic 1‐aryl‐3‐[3‐(thieno[3,2‐ b ]pyridin‐7‐ylthio)phenyl]ureas 1a–e , prepared earlier by us, on two human breast cancer cell lines of distinct histological types: hormone‐dependent MCF‐7 (ER positive), and hormone independent MDA‐MB‐231 (ER/PR/HER2 negative), this latter being the most aggressive and difficult to treat. Our findings clearly demonstrated that compounds 1a – e suppress breast cancer cell survival, proliferation, migration, and colony formation at very low concentrations, not showing cytotoxicity in normal human mammary cells (MCF‐10A). TUNEL assay demonstrated that compounds 1a – e induced apoptosis in MDA‐MB‐231, but not in MCF‐7 at the concentrations tested. PI3K/Akt and MAPK/Erk cell signaling pathways were investigated using Western blot analysis, revealing that these compounds decrease their activity in both breast cancer cell lines. Compounds 1b (R 2 = F), 1c (R 2 = Me), and 1e (R 1 = Cl, R 2 = CF 3 ) were the most effective particularly in MDA‐MB‐231 cells. Overall, 1c and 1e compounds are the most promising antitumor compounds. These findings, together with the antiangiogenic activity previously described by us, render these compounds a relevant breakthrough for cancer therapy. J. Cell. Biochem. 117: 2791–2799, 2016. © 2016 Wiley Periodicals, Inc.