Mandragora autumnalis: Phytochemical Composition, Antioxidant and Anti-Cancerous Bioactivities on Triple-Negative Breast Cancer Cells

Background: Breast cancer is a common and chronic condition, and despite improvements in diagnosis, treatment, and prevention, the number of cases of breast cancer is rising annually. New therapeutic drugs that target specific checkpoints should be created to fight breast cancer. Mandragora autumnalis is considered one of the most important medicinal plants and has significant cultural value as an herb; however, little is known about its anti-cancerous biological activity and chemopreventive molecular pathways against the triple-negative breast cancer (MDA-MB-231) cell line. Methods: The present study aimed to determine the phytochemical content of Mandragora autumnalis leaves ethanolic extract (MAE), both qualitatively and quantitatively. Evaluations were conducted on its anti-oxidant properties, anti-cancer properties, and underlying molecular mechanisms. Results: Results showed that MAE reduced the viability of MDA-MB-231 cells in a concentration and time-dependent manner. While MAE exhibited radical scavenging activity in the DPPH assay, it also caused an increase in reactive oxygen species (ROS) production in MDA-MB-231 cells, however, the antioxidant N-acetyl cysteine (NAC) blocked this effect. Additionally, MAE caused an increase in the tumor suppressor p53. Moreover, this extract caused a significant decrease in the levels of the cell proliferation marker and the transcription factor , Ki67, MMP-9 and STAT-3 respectively. Also, MAE altered cell cycle, cell migration, angiogenesis, invasion, aggregation, and adhesion to suppress cellular processes linked to metastasis. Conclusions: All of our research points to MAE's potential to function as an anticancer agent and opens up new possibilities for the development of innovative triple-negative breast cancer treatments.