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Isobavachalcone Induces Multiple Cell Death in Human Triple-Negative Breast Cancer MDA-MB-231 Cells

Standardized treatment guidelines and effective drugs are not available for human triple-negative breast cancer (TNBC). Many efforts have recently been exerted to investigate the efficacy of natural compounds as anticancer agents owing to their low toxicity. However, no study has examined the effect...

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Autores principales: Wu, Cheng-Zhu, Gao, Mei-Jia, Chen, Jie, Sun, Xiao-Long, Zhang, Ke-Yi, Dai, Yi-Qun, Ma, Tao, Li, Hong-Mei, Zhang, Yu-Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612085/
https://www.ncbi.nlm.nih.gov/pubmed/36296386
http://dx.doi.org/10.3390/molecules27206787
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author Wu, Cheng-Zhu
Gao, Mei-Jia
Chen, Jie
Sun, Xiao-Long
Zhang, Ke-Yi
Dai, Yi-Qun
Ma, Tao
Li, Hong-Mei
Zhang, Yu-Xin
author_facet Wu, Cheng-Zhu
Gao, Mei-Jia
Chen, Jie
Sun, Xiao-Long
Zhang, Ke-Yi
Dai, Yi-Qun
Ma, Tao
Li, Hong-Mei
Zhang, Yu-Xin
author_sort Wu, Cheng-Zhu
collection PubMed
description Standardized treatment guidelines and effective drugs are not available for human triple-negative breast cancer (TNBC). Many efforts have recently been exerted to investigate the efficacy of natural compounds as anticancer agents owing to their low toxicity. However, no study has examined the effects of isobavachalcone (IBC) on the programmed cell death (PCD) of human triple-negative breast MDA-MB-231 cancer cells. In this study, IBC substantially inhibited the proliferation of MDA-MB-231 cells in concentration- and time-dependent manners. In addition, we found that IBC induced multiple cell death processes, such as apoptosis, necroptosis, and autophagy in MDA-MB-231 cells. The initial mechanism of IBC-mediated cell death in MDA-MB-231 cells involves the downregulation of Akt and p-Akt-473, an increase in the Bax/Bcl-2 ratio, and cleaved caspases-3 induced apoptosis; the upregulation of RIP3, p-RIP3 and MLKL induced necroptosis; as well as a simultaneous increase in LC3-II/I ratio induced autophagy. In addition, we observed that IBC induced mitochondrial dysfunction, thereby decreasing cellular ATP levels and increasing reactive oxygen species accumulation to induce PCD. These results suggest that IBC is a promising lead compound with anti-TNBC activity.
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spelling pubmed-96120852022-10-28 Isobavachalcone Induces Multiple Cell Death in Human Triple-Negative Breast Cancer MDA-MB-231 Cells Wu, Cheng-Zhu Gao, Mei-Jia Chen, Jie Sun, Xiao-Long Zhang, Ke-Yi Dai, Yi-Qun Ma, Tao Li, Hong-Mei Zhang, Yu-Xin Molecules Article Standardized treatment guidelines and effective drugs are not available for human triple-negative breast cancer (TNBC). Many efforts have recently been exerted to investigate the efficacy of natural compounds as anticancer agents owing to their low toxicity. However, no study has examined the effects of isobavachalcone (IBC) on the programmed cell death (PCD) of human triple-negative breast MDA-MB-231 cancer cells. In this study, IBC substantially inhibited the proliferation of MDA-MB-231 cells in concentration- and time-dependent manners. In addition, we found that IBC induced multiple cell death processes, such as apoptosis, necroptosis, and autophagy in MDA-MB-231 cells. The initial mechanism of IBC-mediated cell death in MDA-MB-231 cells involves the downregulation of Akt and p-Akt-473, an increase in the Bax/Bcl-2 ratio, and cleaved caspases-3 induced apoptosis; the upregulation of RIP3, p-RIP3 and MLKL induced necroptosis; as well as a simultaneous increase in LC3-II/I ratio induced autophagy. In addition, we observed that IBC induced mitochondrial dysfunction, thereby decreasing cellular ATP levels and increasing reactive oxygen species accumulation to induce PCD. These results suggest that IBC is a promising lead compound with anti-TNBC activity. MDPI 2022-10-11 /pmc/articles/PMC9612085/ /pubmed/36296386 http://dx.doi.org/10.3390/molecules27206787 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wu, Cheng-Zhu
Gao, Mei-Jia
Chen, Jie
Sun, Xiao-Long
Zhang, Ke-Yi
Dai, Yi-Qun
Ma, Tao
Li, Hong-Mei
Zhang, Yu-Xin
Isobavachalcone Induces Multiple Cell Death in Human Triple-Negative Breast Cancer MDA-MB-231 Cells
title Isobavachalcone Induces Multiple Cell Death in Human Triple-Negative Breast Cancer MDA-MB-231 Cells
title_full Isobavachalcone Induces Multiple Cell Death in Human Triple-Negative Breast Cancer MDA-MB-231 Cells
title_fullStr Isobavachalcone Induces Multiple Cell Death in Human Triple-Negative Breast Cancer MDA-MB-231 Cells
title_full_unstemmed Isobavachalcone Induces Multiple Cell Death in Human Triple-Negative Breast Cancer MDA-MB-231 Cells
title_short Isobavachalcone Induces Multiple Cell Death in Human Triple-Negative Breast Cancer MDA-MB-231 Cells
title_sort isobavachalcone induces multiple cell death in human triple-negative breast cancer mda-mb-231 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612085/
https://www.ncbi.nlm.nih.gov/pubmed/36296386
http://dx.doi.org/10.3390/molecules27206787
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