Abstract:
Lung cancer is one of leading cause of deaths worldwide due to cancer metastasis. The metastatic process that initiated by dissociation of cancer cells from the primary tumor and colonization of new tumor at distant organ. Cell migration and invasion play as the key early steps and required actin reorganization and extracellular matrix (ECM) degradation to achieve cell metastasis. The inhibition of these behaviors is an intriguing approach to minimize cancer metastasis. Erianthridin, a phenolic compound isolated from the Thai orchid Dendrobium formosum exhibits several pharmacological activities; however, the effect of erianthridin on lung cancer cell metastasis has not been observed. In this study, we demonstrated that non-toxic and non-proliferative concentrations of erianthridin was able to attenuate cell migration and invasion by disruption of actin stress fibers and lamellipodia formation. The mRNA level of MMP-2 and MMP-9, the matrix-degrading protease, were significantly decreased in a dose-dependent manner after erianthridin treatment. Mechanistic investigation revealed that the active form of Akt and its downstream effectors mTOR and p70S6K were strongly suppressed in the presence of erianthridin. In addition, an in-silico study revealed that erianthridin bound directly at the ATP-bonding site of Akt with both hydrogen bonding and van der Waals interaction, resulting in dephosphorylation of Akt. This study provides preclinical information of erianthridin which exhibits a promising anti-metastasis activity against lung cancer.
