Procaine Abrogates the Epithelial-Mesenchymal Transition Process through Modulating c-Met Phosphorylation in Hepatocellular Carcinoma.
Min Hee YangChakrabhavi Dhananjaya MohanAmudha DeivasigamaniArunachalam ChinnathambiSulaiman Ali AlharbiKanchugarakoppal S RangappaSang Hoon JungHyejin KoKam Man HuiGautam SethiYeong Shik KimPublished in: Cancers (2022)
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.
Keyphrases
- epithelial mesenchymal transition
- signaling pathway
- induced apoptosis
- cell cycle arrest
- pi k akt
- dna methylation
- mouse model
- transforming growth factor
- poor prognosis
- tyrosine kinase
- endoplasmic reticulum stress
- diabetic rats
- gene expression
- oxidative stress
- high glucose
- stem cells
- drug induced
- cell therapy
- young adults
- protein kinase