Monacolin K Induces Apoptosis of Human Glioma U251 Cells by Triggering ROS-Mediated Oxidative Damage and Regulating MAPKs and NF-κB Pathways

Monacolin K (MK), a polyketo secondary metabolic compound of the mold genus Monascus, can promote the apoptosis of malignant cancer cells, possessing potential antitumor properties. However, its mechanism of action on gliomas remains unclear. Here, we explored and investigated the potential of the monacolin K's antitumor effect on human glioma U251 cells and its possible molecular mechanism. Results showed that the application of 10 μM monacolin K inhibited the proliferation of U251 cells, with an inhibitory rate of up to 53.4%. Additionally, monacolin K induced the generation of reactive oxygen species and activated mitochondria-mediated pathways, including decreased MMP, activation of caspase3/caspase9, decreased Na⁺/K⁺-ATPase and Ca²⁺-ATPase activities, and disruption of the antioxidant system, resulting in the disruption of intracellular reduction-oxidation homeostasis. Monacolin K also activated MAPK and NF-κB pathways, upregulating P38 activity and downregulating JNK/ERK/P65/IκBα expression, ultimately leading to apoptosis of U251 cells. Importantly, monacolin K was not cytotoxic to normal human cells, hUC-MSCs. We concluded that monacolin K can induce apoptosis in U251 cells by triggering ROS-mediated oxidative damage and regulating MAPKs and NF-κB pathways.