Curcumin Nanoparticle Induces Apoptosis in Colon Cancer Cells via ROS-Mediated AMPK/mTOR/ULK1 Autophagy Pathway

Curcumin, a highly hydrophobic phenolic compound, has demonstrated potent anticancer activity. However, poor water solubility and a short biological half-life hinder its clinical application. We developed Curcumin-loaded Pluronic F-127 nanoparticles to enhance the bioavailability of Curcumin. It has been reported that excessive autophagy is considered to be the main mechanism of death of various cancer cells. The aim of this study is to investigate whether the Curcumin-loaded Pluronic F-127 nanoparticles exert anti-colon cancer effects by modulating autophagy and explore the specific regulatory mechanism. The proliferative, migratory and apoptotic activity of CT26 cells was assessed by CCK-8 assay, wound healing assay and flow cytometry, respectively. In addition, levels of reactive oxygen species (ROS) were examined by DCFH-DA assay in vitro. ATP levels were detected by the ELISA. The expression levels of autophagy-related proteins and apoptosis-related proteins were visualized by western blotting. Curcumin-loaded Pluronic F-127 nanoparticle inhibited the proliferation of CT26 cells and the growth of colon tumours by promoting cellular autophagy. In addition, Curcumin-loaded Pluronic F-127 nanoparticle reduced mitochondrial membrane potential and impaired mitochondrial function by increasing ROS levels, disrupting ATP biosynthesis. Then the decreased ATP/AMP ratio activated the AMPK/mTOR/ULK1 autophagy signalling pathway and induced autophagy-dependent apoptosis in CT26 cells. Intriguingly, the apoptosis and excessive autophagy induced by Curcumin-loaded Pluronic F-127 nanoparticle were reversed after pretreatment with the antioxidant N-acetyl-L-cysteine. Curcumin-loaded Pluronic F-127 nanoparticle induced autophagy-dependent apoptosis through ROS-AMPK/mTOR/ULK1 signalling in colon cancer cells. Our study offers new insights for colon cancer treatment advancement.