Withanolide C Inhibits Proliferation of Breast Cancer Cells via Oxidative Stress-Mediated Apoptosis and DNA Damage
Some withanolides, particularly the family of steroidal lactones, show anticancer effects, but this is rarely reported for withanolide C (WHC)—especially anti-breast cancer effects. The subject of this study is to evaluate the ability of WHC to regulate the proliferation of breast cancer cells, usin...
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| Format: | Article |
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MDPI AG
2020-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/9/873 |
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| author | Tzu-Jung Yu Jen-Yang Tang Li-Ching Lin Wan-Ju Lien Yuan-Bin Cheng Fang-Rong Chang Fu Ou-Yang Hsueh-Wei Chang |
| author_facet | Tzu-Jung Yu Jen-Yang Tang Li-Ching Lin Wan-Ju Lien Yuan-Bin Cheng Fang-Rong Chang Fu Ou-Yang Hsueh-Wei Chang |
| author_sort | Tzu-Jung Yu |
| collection | DOAJ |
| description | Some withanolides, particularly the family of steroidal lactones, show anticancer effects, but this is rarely reported for withanolide C (WHC)—especially anti-breast cancer effects. The subject of this study is to evaluate the ability of WHC to regulate the proliferation of breast cancer cells, using both time and concentration in treatment with WHC. In terms of ATP depletion, WHC induced more antiproliferation to three breast cancer cell lines, SKBR3, MCF7, and MDA-MB-231, than to normal breast M10 cell lines. SKBR3 and MCF7 cells showing higher sensitivity to WHC were used to explore the antiproliferation mechanism. Flow cytometric apoptosis analyses showed that subG1 phase and annexin V population were increased in breast cancer cells after WHC treatment. Western blotting showed that cleaved forms of the apoptotic proteins poly (ADP-ribose) polymerase (c-PARP) and cleaved caspase 3 (c-Cas 3) were increased in breast cancer cells. Flow cytometric oxidative stress analyses showed that WHC triggered reactive oxygen species (ROS) and mitochondrial superoxide (MitoSOX) production as well as glutathione depletion. In contrast, normal breast M10 cells showed lower levels of ROS and annexin V expression than breast cancer cells. Flow cytometric DNA damage analyses showed that WHC triggered γH2AX and 8-oxo-2′-deoxyguanosine (8-oxodG) expression in breast cancer cells. Moreover, <i>N</i>-acetylcysteine (NAC) pretreatment reverted oxidative stress-mediated ATP depletion, apoptosis, and DNA damage. Therefore, WHC kills breast cancer cells depending on oxidative stress-associated mechanisms. |
| first_indexed | 2024-03-10T16:17:38Z |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T16:17:38Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-7c84e36e3c1d4cba97ffa6b3d32240f82023-11-20T13:54:46ZengMDPI AGAntioxidants2076-39212020-09-019987310.3390/antiox9090873Withanolide C Inhibits Proliferation of Breast Cancer Cells via Oxidative Stress-Mediated Apoptosis and DNA DamageTzu-Jung Yu0Jen-Yang Tang1Li-Ching Lin2Wan-Ju Lien3Yuan-Bin Cheng4Fang-Rong Chang5Fu Ou-Yang6Hsueh-Wei Chang7Division of Breast Surgery and Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, TaiwanDepartment of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Radiation Oncology, Chi-Mei Foundation Medical Center, Tainan 71004, TaiwanDepartment of Biomedical Science and Environmental Biology, Ph.D Program in Life Sciences, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, TaiwanGraduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDivision of Breast Surgery and Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, TaiwanGraduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, TaiwanSome withanolides, particularly the family of steroidal lactones, show anticancer effects, but this is rarely reported for withanolide C (WHC)—especially anti-breast cancer effects. The subject of this study is to evaluate the ability of WHC to regulate the proliferation of breast cancer cells, using both time and concentration in treatment with WHC. In terms of ATP depletion, WHC induced more antiproliferation to three breast cancer cell lines, SKBR3, MCF7, and MDA-MB-231, than to normal breast M10 cell lines. SKBR3 and MCF7 cells showing higher sensitivity to WHC were used to explore the antiproliferation mechanism. Flow cytometric apoptosis analyses showed that subG1 phase and annexin V population were increased in breast cancer cells after WHC treatment. Western blotting showed that cleaved forms of the apoptotic proteins poly (ADP-ribose) polymerase (c-PARP) and cleaved caspase 3 (c-Cas 3) were increased in breast cancer cells. Flow cytometric oxidative stress analyses showed that WHC triggered reactive oxygen species (ROS) and mitochondrial superoxide (MitoSOX) production as well as glutathione depletion. In contrast, normal breast M10 cells showed lower levels of ROS and annexin V expression than breast cancer cells. Flow cytometric DNA damage analyses showed that WHC triggered γH2AX and 8-oxo-2′-deoxyguanosine (8-oxodG) expression in breast cancer cells. Moreover, <i>N</i>-acetylcysteine (NAC) pretreatment reverted oxidative stress-mediated ATP depletion, apoptosis, and DNA damage. Therefore, WHC kills breast cancer cells depending on oxidative stress-associated mechanisms.https://www.mdpi.com/2076-3921/9/9/873withanolidebreast cancerapoptosisoxidative stressDNA damage |
| spellingShingle | Tzu-Jung Yu Jen-Yang Tang Li-Ching Lin Wan-Ju Lien Yuan-Bin Cheng Fang-Rong Chang Fu Ou-Yang Hsueh-Wei Chang Withanolide C Inhibits Proliferation of Breast Cancer Cells via Oxidative Stress-Mediated Apoptosis and DNA Damage Antioxidants withanolide breast cancer apoptosis oxidative stress DNA damage |
| title | Withanolide C Inhibits Proliferation of Breast Cancer Cells via Oxidative Stress-Mediated Apoptosis and DNA Damage |
| title_full | Withanolide C Inhibits Proliferation of Breast Cancer Cells via Oxidative Stress-Mediated Apoptosis and DNA Damage |
| title_fullStr | Withanolide C Inhibits Proliferation of Breast Cancer Cells via Oxidative Stress-Mediated Apoptosis and DNA Damage |
| title_full_unstemmed | Withanolide C Inhibits Proliferation of Breast Cancer Cells via Oxidative Stress-Mediated Apoptosis and DNA Damage |
| title_short | Withanolide C Inhibits Proliferation of Breast Cancer Cells via Oxidative Stress-Mediated Apoptosis and DNA Damage |
| title_sort | withanolide c inhibits proliferation of breast cancer cells via oxidative stress mediated apoptosis and dna damage |
| topic | withanolide breast cancer apoptosis oxidative stress DNA damage |
| url | https://www.mdpi.com/2076-3921/9/9/873 |
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