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UNBS5162 induces growth inhibition and apoptosis via inhibiting PI3K/AKT/mTOR pathway in triple negative breast cancer MDA-MB-231 cells

UNBS5162, a naphthalimide derivative, has a strong anticancer effect and low clinical hematological toxicity. UNBS5162 has been shown to have an anticancer effect in numerous cancer types, except triple negative breast cancer (TNBC). To explore this issue, TNBC MDA-MB-231 cells were selected, and th...

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Autores principales: Yue, Xin, Li, Mingzhong, Chen, Dongxiang, Xu, Zhenghua, Sun, Shengrong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176139/
https://www.ncbi.nlm.nih.gov/pubmed/30344670
http://dx.doi.org/10.3892/etm.2018.6675
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author Yue, Xin
Li, Mingzhong
Chen, Dongxiang
Xu, Zhenghua
Sun, Shengrong
author_facet Yue, Xin
Li, Mingzhong
Chen, Dongxiang
Xu, Zhenghua
Sun, Shengrong
author_sort Yue, Xin
collection PubMed
description UNBS5162, a naphthalimide derivative, has a strong anticancer effect and low clinical hematological toxicity. UNBS5162 has been shown to have an anticancer effect in numerous cancer types, except triple negative breast cancer (TNBC). To explore this issue, TNBC MDA-MB-231 cells were selected, and the effect of UNBS5162 on their growth, proliferation and motility regulation was investigated in vitro. The results showed that UNBS5162 significantly inhibited the proliferation, migration and invasion of TNBC cells. In addition, the level of pro-apoptosis protein Bcl-2-associated X protein and active caspase-3 increased, but apotptosis regulator BCL-2 decreased in MDA-MB-231 cells after UNBS5162 treatment, which demonstrated UNBS5162 treatment triggered cell apoptosis. Moreover, UNBS5162 reduced the phosphorylation levels of AKT serine/threonine kinase (AKT), mechanistic target of rapamycin kinase (mTOR), P70S6 kinase and eukaryotic translation initiation factor 4E-binding protein 1 in the phosphatidylinositol 3-kinase/AKT/mTOR (PAM) signaling pathway, which plays a critical role in cell proliferation, and apoptosis. Altogether, the results of the present study suggest that UNBS5162 effectively induces the growth inhibition and apoptosis of TNBC cells through regulation of the PAM pathway, which may be a candidate target for TNBC treatment.
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spelling pubmed-61761392018-10-21 UNBS5162 induces growth inhibition and apoptosis via inhibiting PI3K/AKT/mTOR pathway in triple negative breast cancer MDA-MB-231 cells Yue, Xin Li, Mingzhong Chen, Dongxiang Xu, Zhenghua Sun, Shengrong Exp Ther Med Articles UNBS5162, a naphthalimide derivative, has a strong anticancer effect and low clinical hematological toxicity. UNBS5162 has been shown to have an anticancer effect in numerous cancer types, except triple negative breast cancer (TNBC). To explore this issue, TNBC MDA-MB-231 cells were selected, and the effect of UNBS5162 on their growth, proliferation and motility regulation was investigated in vitro. The results showed that UNBS5162 significantly inhibited the proliferation, migration and invasion of TNBC cells. In addition, the level of pro-apoptosis protein Bcl-2-associated X protein and active caspase-3 increased, but apotptosis regulator BCL-2 decreased in MDA-MB-231 cells after UNBS5162 treatment, which demonstrated UNBS5162 treatment triggered cell apoptosis. Moreover, UNBS5162 reduced the phosphorylation levels of AKT serine/threonine kinase (AKT), mechanistic target of rapamycin kinase (mTOR), P70S6 kinase and eukaryotic translation initiation factor 4E-binding protein 1 in the phosphatidylinositol 3-kinase/AKT/mTOR (PAM) signaling pathway, which plays a critical role in cell proliferation, and apoptosis. Altogether, the results of the present study suggest that UNBS5162 effectively induces the growth inhibition and apoptosis of TNBC cells through regulation of the PAM pathway, which may be a candidate target for TNBC treatment. D.A. Spandidos 2018-11 2018-09-03 /pmc/articles/PMC6176139/ /pubmed/30344670 http://dx.doi.org/10.3892/etm.2018.6675 Text en Copyright: © Yue et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Yue, Xin
Li, Mingzhong
Chen, Dongxiang
Xu, Zhenghua
Sun, Shengrong
UNBS5162 induces growth inhibition and apoptosis via inhibiting PI3K/AKT/mTOR pathway in triple negative breast cancer MDA-MB-231 cells
title UNBS5162 induces growth inhibition and apoptosis via inhibiting PI3K/AKT/mTOR pathway in triple negative breast cancer MDA-MB-231 cells
title_full UNBS5162 induces growth inhibition and apoptosis via inhibiting PI3K/AKT/mTOR pathway in triple negative breast cancer MDA-MB-231 cells
title_fullStr UNBS5162 induces growth inhibition and apoptosis via inhibiting PI3K/AKT/mTOR pathway in triple negative breast cancer MDA-MB-231 cells
title_full_unstemmed UNBS5162 induces growth inhibition and apoptosis via inhibiting PI3K/AKT/mTOR pathway in triple negative breast cancer MDA-MB-231 cells
title_short UNBS5162 induces growth inhibition and apoptosis via inhibiting PI3K/AKT/mTOR pathway in triple negative breast cancer MDA-MB-231 cells
title_sort unbs5162 induces growth inhibition and apoptosis via inhibiting pi3k/akt/mtor pathway in triple negative breast cancer mda-mb-231 cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176139/
https://www.ncbi.nlm.nih.gov/pubmed/30344670
http://dx.doi.org/10.3892/etm.2018.6675
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