title: Induction of DNA damage and apoptosis in human leukemia cells by efavirenz.
abstract: As part of the efforts to drug repurposing, some HIV drugs have recently been identified to exert anticancer effects. Selected nucleoside analogues of nucleosidic reverse-transcriptase inhibitors (NRTIs) have been shown to interfere with RNA transcription of HI viruses as well as with the replication of DNA in cancer cells. Non-nucleosidic reverse transcriptase inhibitors (NNRTIs) are believed to have less effects on human DNA replication and, thus, on cancer cell proliferation. Assessment of the effect of the NNRTI efavirenz in human cancer cells, however, revealed a high sensitivity of leukemia cells to this agent at pharmacologically relevant concentrations of less than 10 µg/ml. Cell death induced by efavirenz was caused by apoptosis, as shown by FACScan analysis (Annexin binding) and western blot analysis (cleavage of caspases and PARP). Western blot analyses also revealed a pronounced activation and phosphorylation of the DNA damage marker proteins p53, chk2 and H2AX, indicating DNA replication and genomic integrity as primary targets of efavirenz in leukemia cells.
authors.affiliation: Department of Gynecology and Obstetrics, Division of Infectious Diseases in Obstetrics and Gynecology, Campus Innenstadt, Ludwig-Maximilians University of Munich, D-80337 Munich, Germany.
authors.forename: Ansgar
authors.initials: A
authors.lastname: Brüning
authors.affiliation: Department of Gynecology and Obstetrics, Division of Infectious Diseases in Obstetrics and Gynecology, Campus Innenstadt, Ludwig-Maximilians University of Munich, D-80337 Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Jückstock
authors.affiliation: Department of Gynecology and Obstetrics, Division of Infectious Diseases in Obstetrics and Gynecology, Campus Innenstadt, Ludwig-Maximilians University of Munich, D-80337 Munich, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kost
authors.affiliation: Department of Obstetrics and Gynecology, Democrite University Thrace, 68100 Alexandroupolis, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Tsikouras
authors.affiliation: Department of Gynecology and Obstetrics, Division of Infectious Diseases in Obstetrics and Gynecology, Campus Innenstadt, Ludwig-Maximilians University of Munich, D-80337 Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Weissenbacher
authors.affiliation: Department of Gynecology and Obstetrics, Division of Infectious Diseases in Obstetrics and Gynecology, Campus Innenstadt, Ludwig-Maximilians University of Munich, D-80337 Munich, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Mahner
authors.affiliation: Department of Gynecology and Obstetrics, Division of Infectious Diseases in Obstetrics and Gynecology, Campus Innenstadt, Ludwig-Maximilians University of Munich, D-80337 Munich, Germany.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Mylonas
mesh_terms: D000480:Alkynes; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D048588:Benzoxazines / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D003521:Cyclopropanes; D004249:DNA Damage / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D017382:Reactive Oxygen Species; C098320:efavirenz