Streptomyces hygroscopicus UFPEDA 3370: A valuable source of the potent cytotoxic agent nigericin and its evaluation against human colorectal cancer cells

Chem Biol Interact. 2021 Jan 5:333:109316. doi: 10.1016/j.cbi.2020.109316. Epub 2020 Dec 4.

Abstract

Streptomyces hygroscopicus UFPEDA 3370 was fermented in submerged cultivation and the biomass extract was partitioned, obtaining a fraction purified named EB1. After purification of EB1 fraction, nigericin free acid was obtained and identified. Nigericin presented cytotoxic activity against several cancer cell lines, being most active against HL-60 (human leukemia) and HCT-116 (human colon carcinoma) cell lines, presenting IC50 and (IS) values: 0.0014 μM, (30.0) and 0.0138 μM (3.0), respectively. On HCT-116, nigericin caused apoptosis and autophagy. In this study, nigericin was also screened both in vitro and in silico against a panel of cancer-related kinases. Nigericin was able to inhibit both JAK3 and GSK-3β kinases in vitro and its binding affinities were mapped through the intermolecular interactions with each target in silico.

Keywords: Apoptosis; Autophagy; Natural products; Nigericin; Protein kinases.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Catalytic Domain
  • Cell Line, Tumor
  • Colorectal Neoplasms / pathology*
  • Humans
  • Janus Kinase 3 / antagonists & inhibitors
  • Janus Kinase 3 / chemistry
  • Janus Kinase 3 / metabolism
  • Molecular Docking Simulation
  • Nigericin / chemistry
  • Nigericin / metabolism
  • Nigericin / pharmacology*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / metabolism
  • Protein Kinase Inhibitors / pharmacology*
  • Streptomyces / chemistry*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Janus Kinase 3
  • Nigericin

Supplementary concepts

  • Streptomyces hygroscopicus