Garlic-derived organosulfur compound exerts antitumor efficacy via activation of MAPK pathway and modulation of cytokines in SGC-7901 tumor-bearing mice

Int Immunopharmacol. 2017 Jul;48:135-145. doi: 10.1016/j.intimp.2017.05.004. Epub 2017 May 11.

Abstract

Diallyl trisulfide (DATS), a natural agent derived from garlic, has been tested for its antigastric cancer activities in various preliminary studies. However, more systematic pharmacodymatic (PD) and mechanistic evaluations are clearly needed. The aim of this study was to investigate the antitumor effects of DATS in the treatment of human gastric cancer cell SGC-7901 both in vitro and in vivo using widely recommended study procedures. DATS suppressed cancer cells proliferation and induced cell cycle arrest accompanied by an increase in the expressions of cyclin A2 and cyclin B1 in SGC-7901 cancer cells. DATS also caused an increase in apoptotic cell death, which involved in accumulations of bax, p53, and cytochrome C and reduction of Bcl-2 expressions. Besides, activation of JNK, ERK and p38 phosphorylation in DATS-treated cells suggested that mitogen-activated protein kinase (MAPKs) pathways were involved in DATS-induced apoptosis. Meanwhile, DATS significantly inhibited tumor growth and promoted tumor apoptosis in a xenograft model of gastric cancer cell SGC-7901. DATS inhibited tumor migration and invasion by modulating MMP9 and E-cadherin protein expressions. In addition, DATS treatment evidently increased the cytokine secretions of IL-12, TNF-α and IFN-γ (p<0.05). Biochemical serum analysis and histopathological examination indicated no obvious side effects in major mouse organs. Therefore, our findings provide a framework for further exploration of DATS as a novel chemotherapeutic for human gastric cancer.

Keywords: Apoptosis; Cytokines; Diallyl trisulfide (DATS); Gastric cancer; Metastasis; Mitogen-activated protein kinase (MAPK).

MeSH terms

  • Allyl Compounds* / pharmacology
  • Allyl Compounds* / therapeutic use
  • Allyl Compounds* / toxicity
  • Animals
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Antineoplastic Agents* / toxicity
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cytokines / blood
  • Cytokines / genetics
  • Female
  • Garlic
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • Stomach Neoplasms / blood
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Sulfides* / pharmacology
  • Sulfides* / therapeutic use
  • Sulfides* / toxicity
  • Tumor Burden / drug effects

Substances

  • Allyl Compounds
  • Antineoplastic Agents
  • Cytokines
  • Sulfides
  • diallyl trisulfide