Single agent efficacy of the HDAC inhibitor DATS in preclinical models of glioblastoma

Cancer Chemother Pharmacol. 2018 Dec;82(6):945-952. doi: 10.1007/s00280-018-3684-7. Epub 2018 Sep 12.


Purpose/introduction: Glioblastoma (GB) remains incurable despite aggressive chemotherapy, radiotherapy, and surgical interventions; immunotherapies remain experimental in clinical practice. Relevant preclinical models that can accurately predict tumor response to therapy are equally challenging. This study aimed to validate the effect of the naturally occurring agent diallyl trisulfide (DATS) in human GB in relevant pre-clinical models.

Methods: Ex vivo slice culture, in vivo cell line derived orthotopic xenograft and patient-derived orthotopic xenograft (PDX) animal models of GB were utilized to assess efficacy of treatment with DATS.

Results: Our results showed 72-h treatments of 25 µM DATS induced cell death in ex vivo human GB slice culture. We treated U87MG orthotopic xenograft models (U87MGOX) and patient-derived orthotopic xenograft models (PDX) with daily intraperitoneal injections of DATS for 14 days. Magnetic resonance (MR) imaging of mice treated with DATS (10 mg/kg) demonstrated reduced tumor size at 5 weeks when compared with saline-treated U87MGOX and PDX controls. Hematoxylin (H&E) staining demonstrated dose-dependent reduction in gross tumor volume with decreased proliferation and decreased angiogenesis. Western blotting showed that DATS was associated with increases in histone acetylation (Ac-Histone H3/H4) and activated caspase-3 in this novel preclinical model. Histological assessment and enzyme assays showed that even the highest dose of DATS did not negatively impact hepatic function.

Conclusions: DATS may be an effective and well-tolerated therapeutic agent in preventing tumor progression and inducing apoptosis in human GB.

Keywords: DATS; Diallyl trisulfide; GB; Glioblastoma; Histone deacetylase inhibitor; PDX: patient-derived orthotopic xenograft.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allyl Compounds / administration & dosage
  • Allyl Compounds / therapeutic use*
  • Animals
  • Apoptosis / drug effects
  • Astrocytes / drug effects
  • Astrocytes / pathology
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Glioblastoma / drug therapy*
  • Glioblastoma / enzymology
  • Glioblastoma / pathology
  • Histone Deacetylase Inhibitors / administration & dosage
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Histone Deacetylases / metabolism*
  • Humans
  • Male
  • Mice, SCID
  • Neurons / drug effects
  • Neurons / pathology
  • Sulfides / administration & dosage
  • Sulfides / therapeutic use*
  • Xenograft Model Antitumor Assays


  • Allyl Compounds
  • Histone Deacetylase Inhibitors
  • Sulfides
  • diallyl trisulfide
  • Histone Deacetylases