The Mechanism Research Of Compound C7 Induces Autophagic Cell Death In Tumor Cells By Activating AMPK Pathway Through Targeting RXR?

Retinoid x receptor(RXR)is an important transcriptional factor of the nuclear receptor superfamily,which biological function is closely related to many diseases,such as metabolic diseases and tumors.Efficient regulation of some physiological functions by interacting with other signal proteins in cells,which is the main research direction.Autophagy is a process of self-degradation of cellular components,which is generally due to cellular inner and outer pressure or the effects of cytokines,such as starvation,growth factor deficiency,and pathogen infection.Autophagy defects play an important role in the development of human diseases,including cancer,neurological and infectious diseases.Tumor cells may be induced to autophagic cell death(ACD)that can inhibit the proliferation of tumor cells.ACD may become a new way of tumor therapy.Xanthone compounds are a class of phytochemicals.Research shows that xanthone compounds can activate some regulatory factors and induce autophagy or apoptosis in tumor cells,then inhibit the tumor cell proliferation process and play an efficient role against cancer.Our lab has reported that CF31,a xanthone compound targeted RXRa,can negative regulate tRXR?/PI3K/AKT survival pathway,inducing apoptosis and then killing tumor cells.Based on this,we screened a series of homologs of CF31 by SPR,and finally found that compound C7 activated AMPK through CaMKK?,the AMPK upstream kinase,and induced autophagic cell death in tumor cells finally.In this study,we use RXR?/CaMKK?/AMPK? signaling pathway as the main research direction and autophagic cell death in tumor cells as the main detection index,and hope to find a more effective anticancer lead compound in a series of natural products of xanthone.