Abstract
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.
Highlights
Acute myeloid leukemia (AML) is characterized by excess growth of leukemia cells and loss of normal blood cells
Our aim was to introduce an effective way to explore new anti-leukemia compounds of cyanobacteria isolated from biofilm, symbiotic lichen, mollusk association and brackish water habitats in order to find new drug leads for acute myeloid leukemia (AML) therapy
We have previously found high amounts of the metabolite adenosine in diatoms [30] and cyanobacteria [31], and adenosine can induce AML cell apoptosis [32]
Summary
Acute myeloid leukemia (AML) is characterized by excess growth of leukemia cells and loss of normal blood cells. An inhibitor of the Fms-like tyrosine kinase (FLT3) showed promising activity in treatment trials of patients with acute myeloid leukemia [2]. Gemtuzumab ozogamicin is a drug-linked monoclonal antibody, which is used to treat acute myelogenous leukemia. It was recently tested in a Phase II trial of therapy in older patients with acute myeloid leukemia [4]. There is a need for novel anti-leukemia drugs, to be able to treat patients who tolerate heavy chemotherapy poorly or who are found unsuited for stem cell transplantation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
