Mechanisms Involved in the Anti-Tumor Effects of Toosendanin in Glioma Cells

Abstract

Background: Toosendanin (TSN) is a triterpenoid compound mainly used as an ascaris repellant. Recent studies have shown that it possesses antitumor effects in many types of tumor cells. However, the effects of TSN on glioma cells have rarely been reported. Methods: Different assays were performed to investigate the effects of TSN on the different glioma cell lines including U87MG and LN18. The assays included colony formation, wound healing, and transwell assays. Furthermore, Hoechst 3342 staining, flow cytometry, and western blotting analysis were performed to investigate the apoptotic activities of TSN. Finally, the results were confirmed using a xenograft tumor model that comprised of nude mice. Results: In vitro, the CCK-8 and colony formation assays showed that TSN effectively inhibited glioma cell proliferation. Moreover, the inhibitory effects on glioma cell migration and invasion were demonstrated through the wound healing and transwell assays, respectively. Hoechst 33342 staining, flow cytometry, and western blotting assays demonstrated the significant effect of TSN in the apoptosis induction of glioma cells. Furthermore, the anti-glioma effect of TSN was exerted through the inhibition of the PI3K/Akt/mTOR signaling pathways as demonstrated by western blotting analysis. In addition, the effects of TSN on glioma cell viability, apoptosis, cell cycle arrest, migration, and invasion were reversed by 740Y-P, a PI3K activator. Finally, the mouse xenograft model confirmed the suppressive effect of TSN on tumor growth in vivo. Conclusion: Our results suggest that TSN is a promising chemotherapeutic drug for patients with glioma.

CTPS cytoophidia formation affects cell cycle progression and promotes TSN‑induced apoptosis of MKN45 cells

“…such as colorectal cancer cells and glioma cells (22)(23)(24)(25). Our previous studies demonstrated that TSN induces apoptosis of human gastric cancer MKN45 cells (26) and induces formation of CTPS cytoophidia.…”

Design, Synthesis and Anti‐Tumor Activity Evaluation of Novel 3,4‐(Methylenedioxy)cinnamic Acid Amide‐Dithiocarbamate Derivatives

“…Next, the effect of compound 4a 7 on HeLa cells colony formation was explored to further illustrate the antiproliferative activity [26] . As shown in Figure 3, compared to the control, compound 4a 7 can significantly reduce the formation of HeLa cell colonies in a concentration‐dependent manner.…”