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Open AccessArticle

Withanolide C Inhibits Proliferation of Breast Cancer Cells via Oxidative Stress-Mediated Apoptosis and DNA Damage

1
Division of Breast Surgery and Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
2
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
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Department of Radiation Oncology, Chi-Mei Foundation Medical Center, Tainan 71004, Taiwan
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School of Medicine, Taipei Medical University, Taipei 11031, Taiwan
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Chung Hwa University Medical Technology, Tainan 71703, Taiwan
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Department of Biomedical Science and Environmental Biology, Ph.D Program in Life Sciences, College of Life Sciences, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
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Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
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Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
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Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
*
Authors to whom correspondence should be addressed.
Antioxidants 2020, 9(9), 873; https://doi.org/10.3390/antiox9090873
Received: 21 July 2020 / Revised: 5 September 2020 / Accepted: 14 September 2020 / Published: 16 September 2020
(This article belongs to the Special Issue Redox-Active Molecules as Therapeutic Agents)
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, N-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. View Full-Text
Keywords: withanolide; breast cancer; apoptosis; oxidative stress; DNA damage withanolide; breast cancer; apoptosis; oxidative stress; DNA damage
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MDPI and ACS Style

Yu, T.-J.; Tang, J.-Y.; Lin, L.-C.; Lien, W.-J.; Cheng, Y.-B.; Chang, F.-R.; Ou-Yang, F.; Chang, H.-W. Withanolide C Inhibits Proliferation of Breast Cancer Cells via Oxidative Stress-Mediated Apoptosis and DNA Damage. Antioxidants 2020, 9, 873.

AMA Style

Yu T-J, Tang J-Y, Lin L-C, Lien W-J, Cheng Y-B, Chang F-R, Ou-Yang F, Chang H-W. Withanolide C Inhibits Proliferation of Breast Cancer Cells via Oxidative Stress-Mediated Apoptosis and DNA Damage. Antioxidants. 2020; 9(9):873.

Chicago/Turabian Style

Yu, Tzu-Jung; Tang, Jen-Yang; Lin, Li-Ching; Lien, Wan-Ju; Cheng, Yuan-Bin; Chang, Fang-Rong; Ou-Yang, Fu; Chang, Hsueh-Wei. 2020. "Withanolide C Inhibits Proliferation of Breast Cancer Cells via Oxidative Stress-Mediated Apoptosis and DNA Damage" Antioxidants 9, no. 9: 873.

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