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

Abstract

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 = F), 1c (R = Me), and 1e (R = Cl, R = CF ) 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.

AHNAK suppresses tumour proliferation and invasion by targeting multiple pathways in triple-negative breast cancer

“…Moreover, we identified PI3K/AKT and MAPK/ERK as key signalling pathways involved in the inhibition of tumour cell proliferation mediated by AHNAK. The constitutive activation of PI3K/AKT and MAPK/ERK signalling pathways is an important event in breast cancer, as they regulate multiple cellular processes to promote cancer growth, survival, and metastasis [50, 51]. However, there are several limitations in our study that should be addressed.…”

Solid and aqueous magnetoliposomes as nanocarriers for a new potential drug active against breast cancer

“…Recently, a strong VEGFR-2 inhibition activity, with very low IC 50 values (on the order of 10 nM) was reported for a series of new arylurea derivatives of thienopyridines [29]. Also, a potent antiproliferative activity on two human breast cancer cell lines of distinct types, a hormone-dependent MCF-7 and hormone independent MDA-MB-231 cell lines, was described for this type of compounds [30].…”

“…A new diarylurea derivative of thienopyridine 1 (Figure 1), with potent activity against breast cancer cell lines [30], was incorporated in both types of magnetoliposomes.…”

Magnetoliposomes as carriers for promising antitumor thieno[3,2-b]pyridin-7-arylamines: photophysical and biological studies

“…Thienopyridine derivatives have been reported as possessing antiangiogenic, [16][17][18][19][20][21] antitumor, [21][22][23][24][25][26][27][28][29] or both activities. 30 Among the potential antitumor di(hetero)arylamines in the thieno [3,2-b]pyridine series, prepared earlier by some of us, the ones with an o-methoxy or m-methoxy groups relative to the NH (compounds 1 and 2, Fig. 1) presented the lowest growth inhibitory concentration (GI 50 ) values in several human tumor cell lines, between 0.09 and 0.31 mM for compound 1 and between 1.40 and 5.91 mM for compound 2.…”