Alpinetin promotes Bax translocation, induces apoptosis through the mitochondrial pathway and arrests human gastric cancer cells at the G2/M phase

Mol Med Rep. 2013 Mar;7(3):915-20. doi: 10.3892/mmr.2012.1243. Epub 2012 Dec 18.

Abstract

Alpinetin is a natural flavonoid widely distributed in Zingiberaceae. Previous studies have demonstrated that alpinetin markedly inhibits tumour growth. However, the molecular mechanisms underlying the antitumour effects of alpinetin are unclear. Bcl‑2‑associated X protein (Bax) translocation is known to activate the mitochondrial‑dependent endogenous apoptosis pathway. The aim of the current study was to investigate the roles of Bax and the mitochondrial pathway during alpinetin‑induced gastric cancer cell apoptosis and the effects of alpinetin on the cell cycle. Human gastric cancer cells were treated with various doses of alpinetin and an MTT assay was performed to measure cell viability, flow cytometry to measure the apoptotic rate, changes in the cell cycle and mitochondrial membrane potential and western blot analysis to detect the expression levels of relevant proteins. Results demonstrate that alpinetin induces apoptosis in human gastric cancer cells in a dose‑ and time‑dependent manner. During the early stages of apoptosis, alpinetin may alter mitochondrial membrane potential leading to release of cytochrome c from mitochondria, activation of caspase family members and ultimately apoptosis of human gastric cancer cells. Results of the present study indicate that alpinetin‑induced human gastric cancer cell apoptosis is associated with the mitochondrial pathway.

MeSH terms

  • Antineoplastic Agents, Phytogenic / toxicity*
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cytochromes c / metabolism
  • Flavanones / toxicity*
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • M Phase Cell Cycle Checkpoints / drug effects
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Stomach Neoplasms / metabolism
  • Zingiberaceae / chemistry
  • bcl-2-Associated X Protein / metabolism*

Substances

  • Antineoplastic Agents, Phytogenic
  • Flavanones
  • alpinetin
  • bcl-2-Associated X Protein
  • Cytochromes c
  • Caspases