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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/20/6787 |
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| author | Cheng-Zhu Wu Mei-Jia Gao Jie Chen Xiao-Long Sun Ke-Yi Zhang Yi-Qun Dai Tao Ma Hong-Mei Li Yu-Xin Zhang |
| author_facet | Cheng-Zhu Wu Mei-Jia Gao Jie Chen Xiao-Long Sun Ke-Yi Zhang Yi-Qun Dai Tao Ma Hong-Mei Li Yu-Xin Zhang |
| author_sort | Cheng-Zhu Wu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T19:43:37Z |
| format | Article |
| id | doaj.art-af41ad30cda348e4bc08eb4056b3cc33 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T19:43:37Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-af41ad30cda348e4bc08eb4056b3cc332023-11-24T01:31:11ZengMDPI AGMolecules1420-30492022-10-012720678710.3390/molecules27206787Isobavachalcone Induces Multiple Cell Death in Human Triple-Negative Breast Cancer MDA-MB-231 CellsCheng-Zhu Wu0Mei-Jia Gao1Jie Chen2Xiao-Long Sun3Ke-Yi Zhang4Yi-Qun Dai5Tao Ma6Hong-Mei Li7Yu-Xin Zhang8School of Pharmacy, Bengbu Medical College, 2600 Donghai Road, Bengbu 233030, ChinaSchool of Pharmacy, Bengbu Medical College, 2600 Donghai Road, Bengbu 233030, ChinaSchool of Pharmacy, Bengbu Medical College, 2600 Donghai Road, Bengbu 233030, ChinaSchool of Pharmacy, Bengbu Medical College, 2600 Donghai Road, Bengbu 233030, ChinaSchool of Pharmacy, Bengbu Medical College, 2600 Donghai Road, Bengbu 233030, ChinaSchool of Pharmacy, Bengbu Medical College, 2600 Donghai Road, Bengbu 233030, ChinaSchool of Pharmacy, Bengbu Medical College, 2600 Donghai Road, Bengbu 233030, ChinaSchool of Pharmacy, Bengbu Medical College, 2600 Donghai Road, Bengbu 233030, ChinaAnhui Province Biochemical Pharmaceutical Engineering Technology Research Center, Bengbu 233030, ChinaStandardized 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.https://www.mdpi.com/1420-3049/27/20/6787TNBCnatural productisobavachalconecell deathnecroptosisRIP3 |
| spellingShingle | Cheng-Zhu Wu Mei-Jia Gao Jie Chen Xiao-Long Sun Ke-Yi Zhang Yi-Qun Dai Tao Ma Hong-Mei Li Yu-Xin Zhang Isobavachalcone Induces Multiple Cell Death in Human Triple-Negative Breast Cancer MDA-MB-231 Cells Molecules TNBC natural product isobavachalcone cell death necroptosis RIP3 |
| 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 | TNBC natural product isobavachalcone cell death necroptosis RIP3 |
| url | https://www.mdpi.com/1420-3049/27/20/6787 |
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