Coptisine induces G2/M arrest in esophageal cancer cell via the inhibition of p38/ERK1/2/claudin-2 signaling pathway.

In this study, we treated esophageal cancer (EC) cell lines, TE1 and KYSE450 with coptisine (COP) and investigated the biological effects of COP in EC cells. Our results showed that COP inhibited the cell viability and proliferation of EC cells, and COP induced G2/M phase arrest of EC cells and decreased the expression of claudin-2, p-cdc2, CDK1 and cyclin B1. In addition, we found the reduction of p-p38 and p-ERK1/2 in EC cells treated with COP. The effects of COP on pro-cell cycle arresting were reversed after combined with p38 and ERK1/2 inhibitors. Overall, these findings indicate that COP may possess potential for anti-tumor effects in EC and may contribute to the development as anti-cancer agents.

Suppression of Th17 cell differentiation via sphingosine-1-phosphate receptor 2 by cinnamaldehyde can ameliorate ulcerative colitis.

Ulcerative colitis (UC) is chronic disease characterized by diffuse inflammation of the mucosa of the colon and rectum. Although the etiology is unknown, dysregulation of the intestinal mucosal immune system is closely related to UC. Cinnamaldehyde (CA) is a major active compound from cinnamon, is known as its anti-inflammatory and antibacterial. However, little research focused on its regulatory function on immune cells in UC. Therefore, we set out to explore the modulating effects of CA on immune cells in UC. We found that CA reduced the progression of colitis through controlling the production of proinflammatory cytokines and inhibiting the proportion of Th17 cells. Furthermore, the liquid chromatography-mass spectrometry (LC-MS) method was employed for analyzing and differentiating metabolites, data showed that sphingolipid pathway has a great influence on the effect of CA on UC. Meanwhile, sphingosine-1-phosphate receptor 2 (S1P2) and Rho-GTP protein levels were downregulated in colonic tissues after CA treatment. Moreover, in vitro assays showed that CA inhibited Th17 cell differentiation and downregulated of S1P2 and Rho-GTP signaling. Notably, we found that treatment with S1P2 antagonist (JTE-013) weakened the inhibitory effect of CA on Th17 cells. Furthermore, S1P2 deficiency (S1P2-/-) blocked the effect of CA on Th17 cell differentiation. In addition, CA can also improve inflammation via lncRNA H19 and MIAT. To sum up, this study provides clear evidence that CA can ameliorate ulcerative colitis through suppressing Th17 cells via S1P2 pathway and regulating lncRNA H19 and MIAT, which further supports S1P2 as a potential drug target for immunity-mediated UC.