Cytotoxic Fusicoccane-Type Diterpenoids from Streptomyces violascens Isolated from Ailuropoda melanoleuca Feces

J Nat Prod. 2017 Apr 28;80(4):837-844. doi: 10.1021/acs.jnatprod.6b00676. Epub 2017 Feb 16.

Abstract

Six new fusicoccane-type diterpenoids (2-7) were isolated from the fermentation broth of Streptomyces violascens, which was isolated from Ailuropoda melanoleuca (giant panda) feces. The structures of these new compounds were elucidated by a detailed spectroscopic data and X-ray crystallographic analysis. Compounds 5-7 demonstrated cytotoxicity against five human cancer cell lines, with IC50 values ranging from 3.5 ± 0.7 to 14.1 ± 0.8 μM. Cell adhesion, migration, and invasion assays showed that 6 inhibited the migration and invasion of human hepatocellular carcinoma SMMC7721 cells in a dose-dependent manner. Through further investigation, it was revealed that 6 inhibited the enzymatic activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), in addition to down-regulating the expressions of MMP-2 and MMP-9 at both the protein and mRNA levels to influence the migration and invasion of cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification*
  • Diterpenes / pharmacology*
  • Feces / microbiology*
  • Humans
  • Liver Neoplasms
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Streptomyces / chemistry*
  • Ursidae*

Substances

  • Diterpenes
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9