A7, A Novel Analog of Curcumin, Induces Cell Apoptosis Through Suppressing TGF-βR/MEK/ERK Pathway in A549 Cells

Lung cancer is the leading cause of cancer death worldwide and curcumin is a natural polyphenol product with a diversity of antitumor activities. However, its clinical utility is limited due to its relatively low instability and poor bioavailability. This study evaluates the antitumor activity and the underlying mechanism of eight new curcumin analogs in A549 cells. Cell proliferation, migration and apoptosis were examined, respectively, through MTT assay, clone formation, wound healing, transwell, JC-1 staining, Bcl-2 activity, and caspase 3 activity. Protein levels of TGF-βR, MEK, and ERK were determined via western blotting. The binding mode of the ligand and the receptor was simulated by molecular docking studies. Compound A7 was found as the most potent analog (IC₅₀ = 25.78 μM) compared to curcumin (IC₅₀ = 42.30 μM). A7 exposure suppressed A549 cell migration and induced apoptosis with significant differences. Western blot and molecular docking studies demonstrated that the potential mechanism may relate to regulating the TGF-βR/MEK/ERK signaling pathway. Therefore, inhibiting this signaling pathway may provide a potential therapeutic strategy for lung cancer.