TY - JOUR T1 - Effects of the HIF1 Inhibitor, Echinomycin, on Growth and NOTCH Signalling in Leukaemia Cells JF - Anticancer Research JO - Anticancer Res SP - 3099 LP - 3103 VL - 33 IS - 8 AU - SATORU YONEKURA AU - MAI ITOH AU - YUKI OKUHASHI AU - YUSUKE TAKAHASHI AU - AYA ONO AU - NOBUO NARA AU - SHUJI TOHDA Y1 - 2013/08/01 UR - http://ar.iiarjournals.org/content/33/8/3099.abstract N2 - Aim: To examine the effects of echinomycin, a compound that inhibits DNA-binding activity of hypoxia-inducible factor-1 (HIF1), on leukaemia cell growth. Materials and Methods: Three acute myeloid leukaemia cell lines and three T-lymphoblastic leukaemia cell lines were cultured with echinomycin. Cell growth, mRNA and protein expression levels were examined by WST-1 assay, reverse-transcription polymerase chain reaction and immunoblotting, respectively. Results: HIF1α protein was expressed in all cell lines under normoxia. Treatment with echinomycin suppressed cell growth and induced apoptosis in association with decreased mRNA expression of HIF1 targets, glucose transporter-1 (GLUT1) and B-cell CLL/lymphoma-2 (BCL2). Echinomycin also suppressed the protein expression of NOTCH1, cleaved NOTCH1, v-myc myelocytomatosis viral oncogene homolog (MYC), v-akt murine thymoma viral oncogene homolog-1 (AKT), phosphorylated AKT, mechanistic target of rapamycin (mTOR), and phosphorylated mTOR and increased that of cleaved caspase-3 in some cell lines. Conclusion: Echinomycin suppresses leukaemia cell growth in association with reduced NOTCH1 expression. This is the first report to show that HIF inhibitor treatment suppresses NOTCH1 signalling. HIF inhibitors could be novel candidates for a molecular-targeted therapy against leukaemia. ER -