Study of the PI3K/Akt/mTOR signaling pathway in vitro and molecular docking analysis of periplocin inhibits cell cycle progression and induces apoptosis in MDA‐MB‐231

Abstract

AbstractBreast cancer mainly affects women and is the second leading cause of cancer‐related deaths worldwide. Breast cancer affects women aged 15–59. The current study explored periplocin's anticancer activities against breast cancer MDA‐MB‐231 cells by down‐regulating the PI3K/Akt/mTOR pathway. The MTT assay assessed control‐treated and periplocin (2.5–50 μM) treated MDA‐MB‐231 cell viability. ROS accumulation and apoptosis levels in periplocin‐treated cells were examined using DAPI, dual staining, and Annexin V‐FITC/PI assays. Caspase enzymes were studied using assay kits. Flow cytometry was used to measure cell cycle distributions. Periplocin‐treated cells were analyzed using RT‐PCR assays and insilico analyses for the expression of PI3K/Akt/mTOR molecules. The periplocin treatment remarkably reduced the viability of the MDA‐MB‐231 cells, with an IC50 concentration of 7.5 μM. The fluorescent staining assays revealed a substantial increase in ROS levels and apoptotic events in the periplocin‐treated cells. The flow cytometry analysis revealed that periplocin triggered apoptosis and arrested the cell cycle in G0/G1 phases. Periplocin increased the caspase‐3, ‐8, and ‐9 enzyme activities. In MDA‐MB‐231 cells, Periplocin decreased PI3K/Akt/mTOR activity, and in silico analysis, Periplocin was inhibited by CDK8‐Cyclin C interactions. Periplocin has anticancer properties against breast cancer and may be an effective therapeutic agent for treating breast cancer.