Specific RSK kinase inhibition by dibenzyl trisulfide and implication for therapeutic treatment of cancer

Anticancer Res. 2014 Apr;34(4):1637-41.

Abstract

Background/aim: The Jamaican "Guinea Hen Weed" (Petiveria alliacea L.) plant has been traditionally used in folklore medicine to treat a variety of diseases including cancer. In the present study we investigated on the therapeutic feasibility of dibenzyl trisulfide (DTS) (isolated from the Jamaican Guinea Hen Weed) as a potent small-molecule kinase inhibitor to treat cancer.

Materials and methods: We investigated the inhibitory effects of DTS against a large panel of kinases using a well-established competitive binding assay. Cell proliferation data were obtained using the WST-1 colorimetric assay.

Results: DTS inhibited the activity of the C-terminal kinase domain of RSK1 (80% compared to control) with a Kd of 1.3 μM. Anti-proliferative effects of DTS were observed in small lung, pancreatic, breast, and prostate cancer cells with IC50 values ranging from 0.34-0.84 μM.

Conclusion: We have identified DTS as a highly selective and isoform-specific RSK1 kinase inhibitor with broad cancer therapeutic potential.

Keywords: Jamaican Guinea Hen weed; Petiveria alliacea; RSK; cancer; dibenzyl trisulfide; kinase inhibitor.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / toxicity
  • Benzyl Compounds / chemistry
  • Benzyl Compounds / pharmacology*
  • Benzyl Compounds / toxicity
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Humans
  • Neoplasms / metabolism*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / toxicity
  • Ribosomal Protein S6 Kinases / antagonists & inhibitors*
  • Sulfides / chemistry
  • Sulfides / pharmacology*
  • Sulfides / toxicity

Substances

  • Antineoplastic Agents
  • Benzyl Compounds
  • Protein Kinase Inhibitors
  • Sulfides
  • dibenzyl trisulfide
  • Ribosomal Protein S6 Kinases