Cyanobacteria from Terrestrial and Marine Sources Contain Apoptogens Able to Overcome Chemoresistance in Acute Myeloid Leukemia Cells

Autor(es)

Liu, Liwei ^[1] ; Herfindal, Lars ^{[2, 3]} ; Jokela, Jouni ^[1] ; Shishido, Tania Keiko ^[1] ; Wahlsten, Matti ^[1] ; Doskeland, Stein Ove ^[2] ; Sivonen, Kaarina ^[1]

Afiliação do(s) autor(es)

^[1] Univ Helsinki, Div Microbiol & Biotechnol, Dept Food & Environm Sci, Helsinki 00014 - Finland

^[2] Univ Bergen, Dept Biomed, N-5009 Bergen - Norway

^[3] Haukeland Hosp, Translat Signaling Grp, N-5009 Bergen - Norway

• Tipo de documento: Artigo Científico
• Fonte: MARINE DRUGS; v. 12, n. 4, p. 2036-2053, APR 2014.
• Citações Web of Science: 4

Resumo

In this study, we investigated forty cyanobacterial isolates from biofilms, gastropods, brackish water and symbiotic lichen habitats. Their aqueous and organic extracts were used to screen for apoptosis-inducing activity against acute myeloid leukemia cells. A total of 28 extracts showed cytotoxicity against rat acute myeloid leukemia (IPC-81) cells. The design of the screen made it possible to eliminate known toxins, such as microcystins and nodularin, or known metabolites with anti-leukemic activity, such as adenosine and its analogs. A cytotoxicity test on human embryonic kidney (HEK293T) fibroblasts indicated that 21 of the 28 extracts containing anti-acute myeloid leukemia (AML) activity showed selectivity in favor of leukemia cells. Extracts L26-O and L30-O were able to partly overcome the chemotherapy resistance induced by the oncogenic protein Bcl-2, whereas extract L1-O overcame protection from the deletion of the tumor suppressor protein p53. In conclusion, cyanobacteria are a prolific resource for anti-leukemia compounds that have potential for pharmaceutical applications. Based on the variety of cellular responses, we also conclude that the different anti-leukemic compounds in the cyanobacterial extracts target different elements of the death machinery of mammalian cells. (AU)

• Processo FAPESP: 09/13455-0 - Cianobactérias no bioma caatinga: isolamento, morfologia, filogenia e bioprospecção
• Beneficiário: Tânia Keiko Shishido
• Modalidade de apoio: Bolsas no Brasil - Doutorado