Focal adhesion kinase (FAK) controls several
cancer aggressive potentials of cell movement and dissemination. As epithelial-mesenchymal transition (EMT) and the migratory-associated
integrins, known influencers of
metastasis, have been found to be linked with FAK activity, this study unraveled the potential pharmacological effect of
artocarpin in targeting FAK resulting in the suppression of EMT and migratory behaviors of
lung cancer cells. Treatment with
artocarpin was applied at concentrations of 0-10 μM, and the results showed non-cytotoxicity in
lung cancer cell lines (A549 and H460), normal lung (BEAS-2B) cells and primary metastatic
lung cancer cells (ELC12, ELC16, and ELC20). We also found that
artocarpin (0-10 µM) had no effect on cell viability, proliferation, and migration in BEAS-2B cells. For
metastasis-related approaches,
artocarpin significantly inhibited cell migration, invasion, and filopodia formation.
Artocarpin also dramatically suppressed anchorage-independent growth, cancer stem cell (CSC) spheroid formation, and viability of CSC-rich spheroids. For molecular targets of
artocarpin action, computational molecular docking revealed that
artocarpin had the best binding affinity of -8.0 kcal/mol with FAK
protein. Consistently, FAK-downstream
proteins, namely active Akt (phosphorylated Akt), active mTOR (phosphorylated mTOR), and Cdc42, and EMT marker and
transcription factor (
N-cadherin,
Vimentin, and Slug), were found to be significantly depleted in response to
artocarpin treatment. Furthermore, we found the decrease of
Caveolin-1 (Cav-1) accompanied by the reduction of
integrin-αν and integrin-β3. Taken together, these findings support the anti-
metastasis potentials of the compound to be further developed for
cancer therapy.