Telekin suppresses human hepatocellular carcinoma cells in vitro by inducing G2/M phase arrest via the p38 MAPK signaling pathway

Abstract

Aim: Telekin, isolated from the Chinese herb Carpesium divaricatum, has shown anti-proliferation effects against various cancer cells, including hepatocellular carcinoma cells. In this study, we investigated the anti-proliferation mechanisms of telekin in human hepatocellular carcinoma HepG2 cells in vitro. Methods: HepG2 cells were treated with telekin. Cell viability was evaluated using MTT assay. Flow cytometry was used to measure cell cycle profiles, ROS level and apoptosis. The protein expression levels were analyzed with Western blotting. Results: Telekin (3.75-30 µmol/L) dose-dependently inhibited the viability of HepG2 cells and induced l apoptosis. Furthermore, the treatment induced cell cycle arrest at G 2 /M phase, accompanied by significantly increased the phosphorylation of Cdc25A and Cdc2, and decreased Cyclin B1 level. Moreover, the treatment significantly stimulated ROS production, and increased the phosphorylation of p38 and MAPKAPK-2 in the cells. Pretreatment with the antioxidant NAC (2.5, 5, and 10 mmol/L), or the p38 MAPK inhibitor SB203580 (2.5 and 5 µmol/L) dose-dependently attenuated these telekin-induced effects in the cells. Conclusion: Telekin suppresses hepatocellular carcinoma cells in vitro by inducing G 2 /M phase arrest via activating the p38 MAPK pathway.

Diagnostic value of strand‐specific miRNA‐101‐3p and miRNA‐101‐5p for hepatocellular carcinoma and a bioinformatic analysis of their possible mechanism of action

“…These results reveal that miR‐101 probably contributes to the tumorigenesis and metastasis of HCC. Previous studies have reported the role of these pathways in liver cancer . The GO term analysis indicated that these potential target genes of miR‐101‐3p/5p were significantly involved in the regulation of the cell cycle and cell proliferation, which are associated with tumor occurrence or stepwise development.…”

Actinomycin V Suppresses Human Non-Small-Cell Lung Carcinoma A549 Cells by Inducing G2/M Phase Arrest and Apoptosis via the p53-Dependent Pathway

“…CDKs usually interact with cyclin proteins to perform their functions in regulating the cell cycle. In particular, the Cdc2/Cyclin B1 complexes are recognized as the M-phase-related protein in eukaryotic cells [22]. Actinomycin V induced phosphor-Cdc2 but reduced Cyclin B1 and Cdc2 expressions, thereby leading to cell cycle arrest in G2 phase without entering the M phase.…”

Apoptotic Pathway as the Therapeutic Target for Anticancer Traditional Chinese Medicines

“…Studies have shown that telekin at 2.5–10 µmol/L could significantly inhibit the cell proliferation by inducing cellular apoptosis via decreasing the expressions of Bcl-2 and Apaf-1, increasing the expression of Bax, releasing Cyt-c, and activating caspases-9 and -3 in liver cancer HepG2 cells (Zheng B. et al, 2013). Additional studies also showed that Telekin displayed potent cytotoxicity and induced apoptosis against multiple cancer cells (Li et al, 2014; Wang X. et al, 2015). The chemical structures of active compounds from anticancer TCMs that affect Bcl-2/Bax signaling pathway are illustrated in Figure 3 .…”