Baicalin Enhances Chemosensitivity to Doxorubicin in Breast Cancer Cells via Upregulation of Oxidative Stress-Mediated Mitochondria-Dependent Apoptosis
Doxorubicin (Dox) is an effective anthracycline anticancer drug. However, recent studies have revealed that Dox resistance is a highly critical issue, and a significant reason for treatment failure. Baicalin is a flavonoid component in the roots of <i>Scutellaria baicalensis</i> Georgi;...
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MDPI AG
2021-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/10/1506 |
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| author | Mei-Yi Lin Wan-Ting Cheng Hui-Ching Cheng Wan-Ching Chou Hsiu-I Chen Hsiu-Chung Ou Kun-Ling Tsai |
| author_facet | Mei-Yi Lin Wan-Ting Cheng Hui-Ching Cheng Wan-Ching Chou Hsiu-I Chen Hsiu-Chung Ou Kun-Ling Tsai |
| author_sort | Mei-Yi Lin |
| collection | DOAJ |
| description | Doxorubicin (Dox) is an effective anthracycline anticancer drug. However, recent studies have revealed that Dox resistance is a highly critical issue, and a significant reason for treatment failure. Baicalin is a flavonoid component in the roots of <i>Scutellaria baicalensis</i> Georgi; however, whether baicalin can increase chemosensitivity in breast cancers is still unclear. In this study, we found that cellular apoptosis occurs when excessive intracellular ROS is generated, triggered by the dual intervention of baicalin and doxorubicin, which increases intracellular calcium [Ca<sup>2+</sup>]<sub>i</sub> concentrations. Increased [Ca<sup>2+</sup>]<sub>i</sub> concentrations decrease the mitochondrial membrane potential (△Ψ<sub>m</sub>), thereby causing cellular apoptosis. Pretreatment with NAC (ROS inhibitor) or BATBA (Ca<sup>2+</sup> chelator) reduces baicalin-induced chemosensitivity. The findings of this study demonstrate that the effect of baicalin on Dox treatment could enhance cytotoxicity toward breast cancer cells via the ROS/[Ca<sup>2+</sup>]<sub>i</sub>-mediated intrinsic apoptosis pathway—thus potentially lessening the required dosage of doxorubicin, and further exploring associated mechanisms in combined treatments for breast cancer clinical interventions in the future. |
| first_indexed | 2024-03-10T06:46:28Z |
| format | Article |
| id | doaj.art-93e5947fb2414b519fade06c72b597a5 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T06:46:28Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-93e5947fb2414b519fade06c72b597a52023-11-22T17:14:58ZengMDPI AGAntioxidants2076-39212021-09-011010150610.3390/antiox10101506Baicalin Enhances Chemosensitivity to Doxorubicin in Breast Cancer Cells via Upregulation of Oxidative Stress-Mediated Mitochondria-Dependent ApoptosisMei-Yi Lin0Wan-Ting Cheng1Hui-Ching Cheng2Wan-Ching Chou3Hsiu-I Chen4Hsiu-Chung Ou5Kun-Ling Tsai6Department of Chinese Medicine, Ditmanson Medical Foundation Chia-yi Christian Hospital, Chiayi 600, TaiwanDepartment of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan 701, TaiwanDepartment of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan 701, TaiwanDepartment of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan 701, TaiwanDepartment of Physical Therapy, College of Medical and Health Science, Asia University, Taichung 413, TaiwanDepartment of Physical Therapy, College of Medical and Health Science, Asia University, Taichung 413, TaiwanDepartment of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan 701, TaiwanDoxorubicin (Dox) is an effective anthracycline anticancer drug. However, recent studies have revealed that Dox resistance is a highly critical issue, and a significant reason for treatment failure. Baicalin is a flavonoid component in the roots of <i>Scutellaria baicalensis</i> Georgi; however, whether baicalin can increase chemosensitivity in breast cancers is still unclear. In this study, we found that cellular apoptosis occurs when excessive intracellular ROS is generated, triggered by the dual intervention of baicalin and doxorubicin, which increases intracellular calcium [Ca<sup>2+</sup>]<sub>i</sub> concentrations. Increased [Ca<sup>2+</sup>]<sub>i</sub> concentrations decrease the mitochondrial membrane potential (△Ψ<sub>m</sub>), thereby causing cellular apoptosis. Pretreatment with NAC (ROS inhibitor) or BATBA (Ca<sup>2+</sup> chelator) reduces baicalin-induced chemosensitivity. The findings of this study demonstrate that the effect of baicalin on Dox treatment could enhance cytotoxicity toward breast cancer cells via the ROS/[Ca<sup>2+</sup>]<sub>i</sub>-mediated intrinsic apoptosis pathway—thus potentially lessening the required dosage of doxorubicin, and further exploring associated mechanisms in combined treatments for breast cancer clinical interventions in the future.https://www.mdpi.com/2076-3921/10/10/1506doxorubicinbaicalinchemosensitivityROSapoptosis |
| spellingShingle | Mei-Yi Lin Wan-Ting Cheng Hui-Ching Cheng Wan-Ching Chou Hsiu-I Chen Hsiu-Chung Ou Kun-Ling Tsai Baicalin Enhances Chemosensitivity to Doxorubicin in Breast Cancer Cells via Upregulation of Oxidative Stress-Mediated Mitochondria-Dependent Apoptosis Antioxidants doxorubicin baicalin chemosensitivity ROS apoptosis |
| title | Baicalin Enhances Chemosensitivity to Doxorubicin in Breast Cancer Cells via Upregulation of Oxidative Stress-Mediated Mitochondria-Dependent Apoptosis |
| title_full | Baicalin Enhances Chemosensitivity to Doxorubicin in Breast Cancer Cells via Upregulation of Oxidative Stress-Mediated Mitochondria-Dependent Apoptosis |
| title_fullStr | Baicalin Enhances Chemosensitivity to Doxorubicin in Breast Cancer Cells via Upregulation of Oxidative Stress-Mediated Mitochondria-Dependent Apoptosis |
| title_full_unstemmed | Baicalin Enhances Chemosensitivity to Doxorubicin in Breast Cancer Cells via Upregulation of Oxidative Stress-Mediated Mitochondria-Dependent Apoptosis |
| title_short | Baicalin Enhances Chemosensitivity to Doxorubicin in Breast Cancer Cells via Upregulation of Oxidative Stress-Mediated Mitochondria-Dependent Apoptosis |
| title_sort | baicalin enhances chemosensitivity to doxorubicin in breast cancer cells via upregulation of oxidative stress mediated mitochondria dependent apoptosis |
| topic | doxorubicin baicalin chemosensitivity ROS apoptosis |
| url | https://www.mdpi.com/2076-3921/10/10/1506 |
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