Physalis peruviana-Derived Physapruin A (PHA) Inhibits Breast Cancer Cell Proliferation and Induces Oxidative-Stress-Mediated Apoptosis and DNA Damage

Antioxidants

Hsueh-Wei Chang¹  Li-Ching Lin²  Fu Ou-Yang³  Bo-Yi Yao⁴  Fang-Rong Chang⁴  Yuan-Bin Cheng⁴  Chia-Hung Yen⁴  Yi-Hong Tsai⁴  Tzu-Jung Yu⁴  Jen-Yang Tang⁵ 

[1] Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;Department of Radiation Oncology, Chi-Mei Foundation Medical Center, Tainan 71004, Taiwan;Division of Breast Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan;Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;School of Post-Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;

关键词: withanolide;    breast cancer;    apoptosis;    oxidative stress;    DNA damage;   

DOI  :  10.3390/antiox10030393

来源: DOAJ

【 摘 要 】

Breast cancer expresses clinically heterogeneous characteristics and requires multipurpose drug development for curing the different tumor subtypes. Many withanolides have been isolated from Physalis species showing anticancer effects, but the anticancer function of physapruin A (PHA) has rarely been investigated. In this study, the anticancer properties of PHA in breast cancer cells were examined by concentration and time-course experiments. In terms of cellular ATP content, PHA inhibited the proliferation of three kinds of breast cancer cells: MCF7 (estrogen receptor (ER)+, progesterone receptor (PR)+/−, human epidermal growth factor receptor 2 (HER2)−), SKBR3 (ER−/PR−/HER2+), and MDA-MB-231 (triple-negative). Moreover, PHA induced G2/M arrest in MCF7 and MDA-MB-231 cells. In terms of flow cytometry, PHA induced the generation of reactive oxygen species (ROS), the generation of mitochondrial superoxide, mitochondrial membrane potential depletion, and γH2AX-detected DNA damage in breast cancer MCF7 and MDA-MB-231 cells, which were suppressed by the ROS inhibitor N-acetylcysteine (NAC). In terms of flow cytometry and Western blotting, PHA induced apoptotic expression (annexin V, and intrinsic and extrinsic apoptotic signaling), which was suppressed by NAC and an apoptosis inhibitor (Z-VAD-FMK), in breast cancer cells. Therefore, PHA is a potential anti-breast-cancer natural product that modulates the oxidative-stress response, cell-cycle disturbance, apoptosis, and γH2AX-detected DNA damage.

【 授权许可】

Unknown