Life or death? Autophagy in anticancer therapies with statins and histone deacetylase inhibitors.
Autophagy, which could be either cytoprotective or cytotoxic, is often observed in tumor cells in response to chemotherapy. Understanding the signaling pathways involved in the regulation of autophagy represents a new direction in the development of anticancer therapies. Our recent studies investigate the role of autophagy in the anticancer effects of statins and histone deacetylase: inhibitors (HDACi). Inhibition of autophagy enhances the efficacy of statins, whereas autophagic cell death in cancer cells is induced by HDACi. Here, we will discuss the differential signaling pathways elicited by statins and HDACi. We find that AMPK, cytoplasmic p21 and Akt signaling are crucial determinants of cell fates (i.e., life or death) while autophagy is induced.
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Pei-Ming
PM
Yang
Ching-Chow
CC
Chen
D000263:Adenylate Kinase / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D056572:Histone Deacetylase Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D000263:Adenylate Kinase