Reduced scytonemin isolated from Nostoc commune induces autophagic cell death in human T-lymphoid cell line Jurkat cells

Nostoc commune is a terrestrial benthic blue-green alga that often forms an extended mucilaginous layer on the soil, accumulates on stones and mud in aquatic environments. Reduced-scytonemin (R-scy), isolated from N. commune Vaucher, has been shown to suppress the human T-lymphoid Jurkat cell growth. To reveal the mechanisms underlying the R-scy-mediated inhibition of Jurkat cell growth, we examined cell morphology, DNA fragmentation, and microtubule-associated protein light chain 3 (LC3) modification in these cells. We observed multiple vacuoles as well as the conversion of LC3-I to LC3-II in R-scy-treated cells. These results suggest that the R-scy induced Jurkat cell growth inhibition is attributable to the induction of type II programmed cell death (PCD II; autophagic cell death or autophagy). We further examined the mechanisms underlying R-scy-induced PCDII. The cells treated with R-scy produced large amounts of reactive oxygen species (ROS), leading to the induction of mitochondrial dysfunction. However, the elimination of R-scy-induced ROS by treatment with N-acetyl-l-cysteine (NAC) markedly opposed R-scy-induced PCDII. Based on these results, we conclude that ROS formation plays a critical role in R-scy-induced PCDII.