Viola plant cyclotide vigno 5 induces mitochondria-mediated apoptosis via cytochrome C release and caspases activation in cervical cancer cells

Fitoterapia. 2016 Mar:109:162-8. doi: 10.1016/j.fitote.2015.12.021. Epub 2016 Jan 2.

Abstract

Cyclotides describe a unique cyclic peptide family that displays a broad range of biological activities including uterotonic, anti-bacteria, anti-cancer and anti-HIV. The vigno cyclotides consist of vigno 1-10 were reported recently from Viola ignobilis. In the present study, we examined the effects of vigno 5, a natural cyclopeptide from V. ignobilis, on cervical cancer cells and the underlying mechanisms. We found that vigno 5-treated Hela cells were killed off by apoptosis in a dose-dependent manner within 24h, and were characterized by the appearance of nuclear shrinkage, cleavage of poly (ADP-ribose) polymerase (PARP) and DNA fragmentation. The mitochondrial pathway of apoptosis revealed that cytochrome C is released from mitochondria to cytosol, associated with the activation of caspase-9 and -3, and the cleavage of poly (ADP-ribose) polymerase (PARP). Overall, the results indicate that vigno 5 induces apoptosis in part via the mitochondrial pathway, which is associated with a release of cytochrome C and elevated activity of caspase-9 and -3 in Hela cells.

Keywords: Apoptosis; Cyclotide; Mitochondrial pathway; Vigno 5; Viola ignobilis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Survival / drug effects
  • Cyclotides / chemistry*
  • Cytochromes c / metabolism
  • DNA Fragmentation
  • HeLa Cells
  • Humans
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Molecular Sequence Data
  • Plant Proteins / chemistry
  • Viola / chemistry*

Substances

  • Cyclotides
  • Plant Proteins
  • vigno 5 cyclotide, Viola ignobilis
  • Cytochromes c
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9