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

Abstract

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.

The Marine-Derived Natural Product Epiloliolide Isolated from Sargassum horneri Regulates NLRP3 via PKA/CREB, Promoting Proliferation and Anti-Inflammatory Effects of Human Periodontal Ligament Cells

“…Interest and research in marine natural products continues to this day, and the development of healthy functional foods and pharmacological studies have been conducted [ 19 ]. Various pharmacological effects of marine-derived natural products, such as anti-inflammatory, anti-cancer, wound healing, and antioxidant activities, have been proven [ 20 , 21 , 22 ]. However, further research needs to be conducted to clarify the components, physiology, and pharmacological properties of natural products derived from the ocean that are still unknown.…”

Withaferin a Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress

“…HMOX1 and SOD1 mRNA is overexpressed in response to UVC/Nepenthes extract-induced ROS generation [35]. GSR mRNA expression is upregulated by physapruin A-induced ROS generation in breast cancer cells [42]. High oxidative stress in cultured oocytes results in overexpression of mRNA for CAT, SOD1, SOD2, and GSR antioxidant genes [43].…”

Physalis peruviana L.: perspectiva de aplicabilidade no tratamento de câncer

“…Outro estudo também utilizou o isolado withanolide E contra linhagem renal, e observou um aumento de apoptose pela sensibilização de TRAIL e o aumento da expressão de genes envolvidos na apoptose (pró e anti) e uma ação pró-oxidante (Henrich et al, 2015), essa última ação é bem comum dentre os isolados e também foi observado em outros dois estudo, o de Rao et al (2016) e Yu et al (2021).…”

“…De uso popular, seus farmacógenos são aplicados em várias doenças, como câncer, hepatite e reumatismo, destacando-se na literatura pela composição química, aspecto nutricional e farmacológico. Os frutos são de sabor agradável, semelhante ao de tomate doce, rico em vitamina, vitamina A e vitaminas do complexo B, (Franco et al, 2006;Huang et al, 2020;Puente, 2011;Rodríguez & Rodríguez, 2007;Vega et al, 2020;Yu et al, 2021).…”

“…Alguns estudos observaram apoptose ativada por sinalização mitocondrial em diferentes vias de sinalização, que demonstra o enorme potencial desta planta em aplicações alimentares e fitoterápicas (Yu et al, 2021;Hsieh et al, 2021;Xu et al, 2021).…”