Iodinin (1,6-Dihydroxyphenazine 5,10-Dioxide) from Streptosporangium sp. Induces Apoptosis Selectively in Myeloid Leukemia Cell Lines and Patient Cells

Marine Drugs

Lene E. Myhren³  Gyrid Nygaard³  Gro Gausdal³  Håvard Sletta²  Knut Teigen³  Kristin F. Degnes²  Kolbjørn Zahlsen²  Anders Brunsvik²  Øystein Bruserud¹  Stein Ove Døskeland³  Frode Selheim³ 

[1] Section for Haematology, Institute of Medicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway; E-Mail:;SINTEF Materials and Chemistry, Department of Biotechnology, Sem Sælands vei 2a, N-7465 Trondheim, Norway; E-Mails:;Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway; E-Mails:

关键词: acute myeloid leukemia;    natural products;    daunorubicin;    patient samples;   

DOI  :  10.3390/md11020332

来源: mdpi

【 摘 要 】

Despite recent improvement in therapy, acute myeloid leukemia (AML) is still associated with high lethality. In the presented study, we analyzed the bioactive compound iodinin (1,6-dihydroxyphenazine 5,10-dioxide) from a marine actinomycetes bacterium for the ability to induce cell death in a range of cell types. Iodinin showed selective toxicity to AML and acute promyelocytic (APL) leukemia cells, with EC50 values for cell death up to 40 times lower for leukemia cells when compared with normal cells. Iodinin also successfully induced cell death in patient-derived leukemia cells or cell lines with features associated with poor prognostic such as FLT3 internal tandem duplications or mutated/deficient p53. The cell death had typical apoptotic morphology, and activation of apoptotic signaling proteins like caspase-3. Molecular modeling suggested that iodinin could intercalate between bases in the DNA in a way similar to the anti-cancer drug daunorubicin (DNR), causing DNA-strand breaks. Iodinin induced apoptosis in several therapy-resistant AML-patient blasts, but to a low degree in peripheral blood leukocytes, and in contrast to DNR, not in rat cardiomyoblasts. The low activity towards normal cell types that are usually affected by anti-leukemia therapy suggests that iodinin and related compounds represent promising structures in the development of anti-cancer therapy.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.