title: Specific RSK kinase inhibition by dibenzyl trisulfide and implication for therapeutic treatment of cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  We have identified DTS as a highly selective and isoform-specific RSK1 kinase inhibitor with broad cancer therapeutic potential.
authors.affiliation: 39 Lady Musgrave Road, Kingston 5, Jamaica, W.I. henrylowe@cwjamaica.com; lowebiotech@gmail.com.
authors.forename: Henry I C
authors.initials: HI
authors.lastname: Lowe
authors.forename: Caroline O B
authors.initials: CO
authors.lastname: Facey
authors.forename: Ngeh J
authors.initials: NJ
authors.lastname: Toyang
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Bryant
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001593:Benzyl Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D019893:Ribosomal Protein S6 Kinases / Q000037:antagonists & inhibitors*; D013440:Sulfides / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D001593:Benzyl Compounds; D047428:Protein Kinase Inhibitors; D013440:Sulfides; C495415:dibenzyl trisulfide; D019893:Ribosomal Protein S6 Kinases
keywords: Jamaican Guinea Hen weed; Petiveria alliacea; RSK; cancer; dibenzyl trisulfide; kinase inhibitor