Sideroxylin (Callistemon lanceolatus) suppressed cell proliferation and increased apoptosis in ovarian cancer cells accompanied by mitochondrial dysfunction, the generation of reactive oxygen species, and an increase of lipid peroxidation

J Cell Physiol. 2018 Nov;233(11):8597-8604. doi: 10.1002/jcp.26540. Epub 2018 Jun 15.

Abstract

Sideroxylin is a C-methylated flavone isolated from Callistemon lanceolatus and exerts antimicrobial activity against Staphylococcus aureus. However, the anticancer effects of sideroxylin and its intracellular signaling mechanisms have not yet been identified. Results of our study showed that sideroxylin decreased cell proliferation and increased apoptosis, causing DNA fragmentation, depolarization of the mitochondrial membrane, the generation of reactive oxygen species, and an increase of lipid peroxidation in ovarian cancer cells (ES2 and OV90 cells). Additionally, sideroxylin activated the phosphorylation of ERK1/2, JNK, P38, and MAPK proteins and the use of LY294002, U0126, SB203580, and SP600125 to block their phosphorylation, respectively, in ES2 and OV90 cells. Collectively, the results of present study indicated that sideroxylin was a novel therapeutic agent to combat the proliferation of ovarian cancer cells through the induction of mitochondrial dysfunction and the activation of PI3 K and MAPK signal transduction.

Keywords: Callistemon lanceolatus; apoptosis; ovarian cancer; sideroxylin; signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Female
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Humans
  • Lipid Peroxidation / drug effects
  • MAP Kinase Signaling System / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / pathology
  • Myrtaceae / chemistry
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Oxidative Stress / drug effects*
  • Phosphorylation / drug effects
  • Reactive Oxygen Species / metabolism

Substances

  • Flavonoids
  • Reactive Oxygen Species
  • sideroxylin