Abstract
After screening marine actinomycetes isolated from sediment samples collected from the Arctic fjord Kongsfjorden for potential anticancer activity, an isolate identified as Streptomyces artemisiae MCCB 248 exhibited promising results against the NCI-H460 human lung cancer cell line. H460 cells treated with the ethyl acetate extract of strain MCCB 248 and stained with Hoechst 33342 showed clear signs of apoptosis, including shrinkage of the cell nucleus, DNA fragmentation and chromatin condensation. Further to this treated cells showed indications of early apoptotic cell death, including a significant proportion of Annexin V positive staining and evidence of DNA damage as observed in the TUNEL assay. Amplified PKS 1 and NRPS genes involved in secondary metabolite production showed only 82% similarity to known biosynthetic genes of Streptomyces, indicating the likely production of a novel secondary metabolite in this extract. Additionally, chemical dereplication efforts using LC–MS/MS molecular networking suggested the presence of a series of undescribed tetraene polyols. Taken together, these results revealed that this Arctic S. artemisiae strain MCCB 248 is a promising candidate for natural products drug discovery and genome mining for potential anticancer agents.
Highlights
Microorganisms have been the source of many chemotherapeutics used in cancer treatment, and amongst them, actinomycetes are the most promising source organisms
Preliminary screening for anticancer activity of the extracts of these isolates resulted in the identification of one isolate, designated as MCCB 248 (Fig. 1), as possessing the most potent growth inhibition against NCIH460 cells (Fig. 2)
NCI-H460 cells exposed to the S. artemisiae MCCB248 extract exhibited a characteristic apoptotic morphology, such as shrinkage of cell nuclei, chromatin condensation and nuclear fragmentation (Fig. 5a, b), which indicated that one or more components of this extract induced apoptosis
Summary
Microorganisms have been the source of many chemotherapeutics used in cancer treatment, and amongst them, actinomycetes are the most promising source organisms. The rate of discovery of new bioactive compounds has reduced, but the rediscovery of known compounds has increased (Fenical et al 1999). There is a need for bioprospecting of unexplored or underexplored habitats for unique and rare microorganisms, as these can be expected to yield a higher percentage of novel metabolites with desirable bioactivities (Bredholt et al 2008; Pathom-aree et al 2006). The Arctic region remains one of the least well-explored geographical locations on Earth for novel bioactive metabolites. We report on the isolation and screening of actinomycetes from sediment collected from an Arctic fjord and discovery of the production of potential anticancer natural products
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