Secondary metabolites from American Samoa cyanobacteria with anticancer potential

Kelsey Alexander
Appointment Period: 2018-2019, Grant Year: [33]

Two different species of cyanobacteria were collected in American Samoa and then further cultured in our laboratory; these have become the focus of this anticancer drug discovery research. The first culture, Leptolyngbya sp., was initially prioritized due to its cytotoxicity against NIH-H460 lung cancer cells. Lung cancer is one of the most prevalent types in both men and women and is the leading cause of cancer death¹ The most polar fraction had cytotoxicity at 10 mg/mL. An LC-MS/MS molecular network was made through GNPS (global natural products social molecular network) to gain insight into the spectrum of metabolites in this culture. Of particular note was a cluster of compounds present in the cytotoxic fraction. This lead to the targeted isolation of one of the compounds present in this fraction. The MS/MS of this ion did not match with anything in the GNPS library, leading to the hypothesis that this is a new compound, and that it is a member of novel family of new compounds as seen by the MS2 molecular networks. Planned future work includes further structure elucidation of already and to-be isolated compounds guided by their toxicity to lung cancer cells.  When these novel lung cancer cytotoxins are fully isolated and their structures characterized, other areas of investigation will become possible, such as spectrum of activity to different cancer cell types, mechanism of action, and identification of the pharmacophore of the molecule.  These marine cyanobacterial natural products offer significant potential for the discovery of a new anticancer drug lead.   

¹Key Statistics for Lung Cancer https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/key-statistics.html (accessed Jul 12, 2018).

PUBLICATIONS (resulting from this training)

Trainee recently appointed to grant: publications are still in progress.