Novel mechanism of harmaline on inducing G2/M cell cycle arrest and apoptosis by up-regulating Fas/FasL in SGC-7901 cells

Sci Rep. 2015 Dec 18;5:18613. doi: 10.1038/srep18613.

Abstract

Harmaline (HAR), a natural occurrence β-carboline alkaloid, was isolated from the seeds of Peganum harmala and exhibited potent antitumor effect. In this study, the anti-gastric tumor effects of HAR were firstly investigated in vitro and in vivo. The results strongly showed that HAR could inhibit tumor cell proliferation and induce G2/M cell cycle arrest accompanied by an increase in apoptotic cell death in SGC-7901 cancer cells. HAR could up-regulate the expressions of cell cycle-related proteins of p-Cdc2, p21, p-p53, Cyclin B and down-regulate the expression of p-Cdc25C. In addition, HAR could up-regulate the expressions of Fas/FasL, activated Caspase-8 and Caspase-3. Moreover, blocking Fas/FasL signaling could markedly inhibit the apoptosis caused by HAR, suggesting that Fas/FasL mediated pathways were involved in HAR-induced apoptosis. Interestingly, HAR could also exert on antitumor activity with a dose of 15 mg/kg/day in vivo, which was also related with cell cycle arrest. These new findings provided a framework for further exploration of HAR which possess the potential antitumor activity by inducing cell cycle arrest and apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Fas Ligand Protein / metabolism*
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Harmaline / chemistry
  • Harmaline / pharmacology*
  • Harmaline / therapeutic use
  • Humans
  • M Phase Cell Cycle Checkpoints / drug effects
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms / drug therapy
  • Peganum / chemistry
  • Peganum / metabolism
  • Seeds / chemistry
  • Seeds / metabolism
  • Signal Transduction / drug effects
  • Up-Regulation* / drug effects
  • fas Receptor / metabolism*

Substances

  • Antineoplastic Agents, Phytogenic
  • FAS protein, human
  • Fas Ligand Protein
  • fas Receptor
  • Harmaline