Obovatol induces apoptosis in breast cancer by downregulating the PI3K/Akt pathway.

BACKGROUND: Obovatol (Ob), extracted from the bark of Magnolia obovata Thunb., originates from a genus with a well-documented history in East Asian traditional medicine for treating ailments characterized by inflammation and neoplastic-like symptoms. Despite preliminary observations suggesting that Ob exerts anti-tumor effects in various cancers, its specific efficacy and underlying mechanisms of action in breast cancer (BC) remain largely unexplored. This study aimed to investigate the anti-tumor efficacy of Ob against BC and to elucidate its underlying molecular mechanisms. METHODS: Cell counting kit-8, Transwell, flow cytometry, and Western blotting (WB) assays were used to examine the effects and functions of Ob on cellular proliferation, invasion, and apoptosis in BC cells (MDA-MB-231 and MDA-MB-468). Bagg Albino/c (BALB/c) nude female mice were applied to evaluate the anti-cancer effects and biosecurity of Ob. Transcriptome sequencing was used to identify the pathway modulated by Ob in BC, and WB assays were then used to validate the key findings. RESULTS: In MDA-MB-231 and MDA-MB-468 cells, Ob decreased the cell viability, exhibiting the half maximal inhibitory concentration (IC(50)) values for 50.97 and 48.29 µM, respectively. Additionally, by upregulating E-cadherin while downregulating N-cadherin and vimentin, Ob reversed the epithelial-mesenchymal transition, thereby significantly inhibiting the migration and invasion of BC cells. Ob led to mitochondrial apoptosis, as shown by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X protein (Bax) and activated caspase-3 levels. Consistent with the in vitro findings, Ob treatment effectively limited tumor growth in the mouse model, demonstrating considerable biological safety. Importantly, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway has been proven to be a key mechanistic target, as Ob suppressed its activation. CONCLUSIONS: By downregulating the PI3K/Akt pathway, Ob reduced cell proliferation and invasion and induced apoptosis in BC.