Procaine Abrogates the Epithelial-Mesenchymal Transition Process through Modulating c-Met Phosphorylation in Hepatocellular Carcinoma
Min Yang, Chakrabhavi Dhananjaya Mohan, Amudha Deivasigamani, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Kanchugarakoppal S. Rangappa, Sang Hoon Jung, Hyejin Ko, Kam M. Hui, Gautam Sethi, Kwang Seok Ahn
Abstract
EMT is a critical cellular phenomenon that promotes tumor invasion and metastasis. Procaine is a local anesthetic agent used in oral surgeries and as an inhibitor of DNA methylation in some types of cancers. In this study, we have investigated whether procaine can inhibit the EMT process in HCC cells and the preclinical model. Procaine suppressed the expression of diverse mesenchymal markers but induced the levels of epithelial markers such as E-cadherin and occludin in HGF-stimulated cells. Procaine also significantly reduced the invasion and migration of HCC cells. Moreover, procaine inhibited HGF-induced c-Met and its downstream oncogenic pathways, such as PI3K/Akt/mTOR and MEK/ERK. Additionally, procaine decreased the tumor burden in the HCC mouse model and abrogated lung metastasis. Overall, our study suggests that procaine may inhibit the EMT process through the modulation of a c-Met signaling pathway.