Natural products derived from marine cyanobacteria as HIF inhibitors. (a) Dose-response curves using isogenic HCT116 cell lines for dolastatin 10 and largazole. (b-d) Largazole (20 nM) downregulated HIF target genes (b) and HIF-1α transcript (c) , and diminished HIF-1α protein (d) based on immunoblot analysis, while HIF-1β (d) was unaltered (16 h treatment). (e) Largazole inhibited HCT116 cell growth in colony formation assays. (f) Largazole demonstrated differential toxicity towards LoVo relative to the HIF-independent cell line, RKO. (g) Largazole inhibited angiogenesis in vitro in a dose-dependent manner, determined by matrigel assay using HUVECs (scale bar 200 μm). (h) Effect of largazole on HUVEC viability and transcripts of pro-angiogenic factors (VEGFA, FGF2) and anti-angiogenic factors (THS2).