Raptor couples mTORC1 and ERK1/2 inhibition by cardamonin with oxidative stress induction in ovarian cancer cells

Background: A balance on nutrient supply and redox homeostasis is required for cell survival, and increased antioxidant capacity of cancer cells may lead to chemotherapy failure.Objective: To investigate the mechanism of anti-proliferation of cardamonin by inducing oxidative stress in ovarian cancer cells.Methods: After 24 h of drug treatment, CCK8 kit and wound healing test were used to detect cell viability and migration ability, respectively, and the ROS levels were detected by flow cytometry. The differential protein expression after cardamonin administration was analyzed by proteomics, and the protein level was detected by Western blotting.Results: Cardamonin inhibited the cell growth, which was related to ROS accumulation. Proteomic analysis suggested that MAPK pathway might be involved in cardamonin-induced oxidative stress. Western blotting showed that cardamonin decreased Raptor expression and the activity of mTORC1 and ERK1/2. Same results were observed in Raptor KO cells. Notably, in Raptor KO cells, the effect of cardamonin was weakened.Conclusion: Raptor mediated the function of cardamonin on cellular redox homeostasis and cell proliferation through mTORC1 and ERK1/2 pathways.

Automated summary

The study found that cardamonin inhibits the proliferation of ovarian cancer cells by inducing oxidative stress. Proteomic analysis and Western blotting revealed that cardamonin affects cellular redox homeostasis and cell proliferation through the MAPK pathway and the mTORC1 and ERK1/2 pathways.