title: Cerulenin-induced apoptosis is mediated by disrupting the interaction             between AIF and hexokinase II.
abstract: Fatty acid synthase (FASN) is a key enzyme that plays a critical role in             numerous metabolic functions by catalyzing the synthesis for long-chain fatty             acids. FASN is highly expressed in various human cancers. This preferential expression             makes FASN an attractive target for anticancer therapy. Hexokinase II (HKII) is             overexpressed in most cancer cells, and it generally localizes to the outer mitochondrial             membrane. Recent studies have demonstrated the protective role of mitochondrial             HKII in preservation of mitochondrial integrity. The association of hexokinase             with mitochondria has emerged as a powerful mechanism in protecting numerous cell             types against cell death. We performed this study to examine the mechanism underlying             apoptosis induced by cerulenin and with specific focus on its effect on HKII in             ZR-75-1 human breast cancer cells. Additionally, we sought to elucidate whether             inhibition of the PI3K/Akt pathway can potentiate the anticancer effect of cerulenin.             Here, we showed that cerulenin disrupts the physical association between HKII             and AIF, leading to eventual cell death. In addition, LY294002, a PI3K/Akt inhibitor,             sensitized ZR-75-1 breast cancer cells to cerulenin-induced apoptosis. Collectively,             cerulenin induces apoptosis via disrupting the interaction between AIF and HKII             and inhibition of PI3K sensitizes cells to cerulenin-induced apoptosis in ZR-75-1             cells.
authors.affiliation: Department of Anatomy and Cell Biology and Mitochondria Hub Regulation                     Center, Dong-A University College of Medicine, Busan, Republic of Korea.
authors.forename: Na Young
authors.initials: NY
authors.lastname: Jeong
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002569:Cerulenin / Q000494:pharmacology*; D002867:Chromones / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004357:Drug Synergism; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051033:Apoptosis Inducing Factor; D051017:Apoptosis Regulatory Proteins; D053148:Caspase 3; D002569:Cerulenin; D002867:Chromones; D045304:Cytochromes c; D006593:Hexokinase; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C494829:AIFM1 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C505407:CASP3 protein, human