Grandiflorenic acid from Wedelia trilobata plant induces apoptosis and autophagy cell death in breast adenocarcinoma (MCF7), lung carcinoma (A549), and hepatocellular carcinoma (HuH7.5) cells lines. (15th October 2022)

• Record Type: Journal Article
• Authors: Fagundes, Tatiane Renata; Taciane da Silva Bortoleti, Bruna; Tomiotto-Pellissier, Fernanda; Concato, Vírgínia Márcia; Gonçalves, Manoela Daiele; Arakawa, Nilton Syogo; Miranda-Sapla, Milena Menegazzo; Panis, Carolina; Pavanelli, Wander Rogério
• Is Part Of: Toxicon. Volume 217(2022)
• Page Start: 112
• Page End: 120
• Publication Date: 2022-10-15
• Subjects: Tumor cells -- Apoptosis -- Autophagy -- ROS -- Grandiflorenic acid; Toxins -- Periodicals; Venom -- Periodicals; 615.9
• DOI: 10.1016/j.toxicon.2022.08.006
• Languages: English
• ISSNs: 0041-0101

Abstract

Abstract: Introduction : Wedelia trilobata (Sphagneticola trilobata) is a plant used in this popular medicine for treating infectious, sores and swellings in some rural communities, and their extract has antioxidant, anti-inflammatory, antitumor and hepatoprotective effect. Cancer is a molecularly heterogeneous disease caused by environmental and, genetic factors, among others. Since the complexity of the disease leads to low response rates to the different treatments used, it is necessary to find alternative drugs aimed at its control. The objective of our study was to assess whether grandiflorenic acid (GFA) has antitumor activity on breast (MCF7), liver (HuH7.5), and lung (A549) tumor cell lines. Methods : We used cell integrity assessment methods to assess whether (GFA) would be cytotoxic for tumor cell lines at doses ranging from and the pattern of death involved in this effect. Results : Treatment using GFA significantly inhibited cell proliferation in the three studied cells, followed by a decrease in cell size. The assessment of the death mechanisms showed the treatments increased the production of reactive oxygen species, caused exposure of phosphatidylserine, depolarization of the mitochondrial membrane, and, decrease plasma membrane integrity, indicating mechanisms related to apoptosis. Besides, we found the formation of autophagy vacuoles in our tests. Conclusion: Finally, our study found the effect of GFA on breast (MCF7), lung (A549), and liver (HuH7.5) tumor cell lines induce cytotoxicity and patterns of death associated with apoptosis and autophagy, and oxidative stress generation plays a role in these two pathways of cell death. Thus, this study revealed GFA exhibits anti-cancer activity in vitro and could help future studies to improve strategies for cancer treatment with involving natural compounds. Graphical abstract: Image 1 Highlights: GFA reduces the viability of HuH7.5, MCF7 and A549 tumor cells. GFA increases ROS levels and alters ΔΨm. GFA promotes autophagic vacuoles, a cell size reduction, and characteristics related to the apoptotic process. GFA treatment induces caspase-3-like proteases.