Anti-tumor effects of Artemisia nilagirica extract on MDA-MB-231 breast cancer cells: deciphering the biochemical and biomechanical properties via TGF-β upregulation

PURPOSE: Artemisia nilagirica (AN), which is known to have antimicrobial, antioxidant, antiulcer, and anti-asthmatic properties, has been recently shown to have anti-cancer activity. However, the mechanism responsible for the anti-cancer property and its effect on cellular properties and functions are not known. MATERIAL AND METHODS: We have characterized the biochemical and biomechanical properties of MDA-MB-231 cells treated with the methanolic extract from AN. RESULTS: We show that AN-treatment decreases cell-eccentricity, increases expression of actin and microtubules, and do not affect cell-area. Increased expression of cytoskeletal proteins is known to change the mechanical properties of the cells, which was confirmed using micropipette aspiration and Atomic Force Microscopy. We identified the upregulation of the tumorigenic pathway (TGF-β) leading to activation of Rho-A as the molecular mechanism responsible for actin upregulation. Since the initial stages of TGF-β upregulation are known to suppress tumor growth by activating apoptosis, we hypothesized that the mechanism of cell death due to AN-treatment is through TGF-β activation. We have validated this hypothesis by partially recuing cell death through inhibition of TGF-β using Alk-5. CONCLUSION: In summary, our study reveals the mechanism of action of Artemisia nilagirica using a synergy between biochemical and biomechanical techniques.