β,β-Dimethylacrylshikonin induces mitochondria dependent apoptosis through ERK pathway in human gastric cancer SGC-7901 cells

PLoS One. 2012;7(7):e41773. doi: 10.1371/journal.pone.0041773. Epub 2012 Jul 27.

Abstract

β,β-Dimethylacrylshikonin, one of the active components in the root extracts of Lithospermum erythrorhizon, posses antitumor activity. In this study, we discussed the molecular mechanisms of β,β-dimethylacrylshikonin in the apoptosis of SGC-7901 cells. β,β-Dimethylacrylshikonin reduced the cell viability of SGC-7901 cells in a dose- and time-dependent manner and induced cell apoptosis. β,β-Dimethylacrylshikonin treatment in SGC-7901 cells down-regulated the expression of XIAP, cIAP-2, and Bcl-2 and up-regulated the expression of Bak and Bax and caused the loss of mitochondrial membrane potential and release of cytochrome c. Additionally, β,β-dimethylacrylshikonin treatment led to activation of caspases-9, 8 and 3, and cleavage of poly (ADP-ribose) polymerase (PARP), which was abolished by pretreatment with the pan-caspase inhibitor Z-VAD-FMK. β,β-Dimethylacrylshikonin induced phosphorylation of extracellular signal-regulated kinase (ERK) in SGC-7901 cells. U0126, a specific MEK inhibitor, blocked the ERK activation by β,β-dimethylacrylshikonin and abrogated β,β-dimethylacrylshikonin -induced apoptosis. Our results demonstrated that β,β-dimethylacrylshikonin inhibited growth of gastric cancer SGC-7901 cells by inducing ERK signaling pathway, and provided a clue for preclinical and clinical evaluation of β,β-dimethylacrylshikonin for gastric cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Enzyme Activation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Humans
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Naphthoquinones / pharmacology*
  • Signal Transduction / drug effects*
  • Stomach Neoplasms / pathology*

Substances

  • Antineoplastic Agents
  • Naphthoquinones
  • beta, beta-dimethylacrylshikonin
  • Extracellular Signal-Regulated MAP Kinases

Grants and funding

This work was supported by grants from Zhejiang Provincial Natural Science Foundation of China to X-QM (LY12H28005), and the science foundation of Zhejiang Chinese Medical University to H-BW (2011ZY05). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.