Diallyl trisulfide induces Bcl-2 and caspase-3-dependent apoptosis via downregulation of Akt phosphorylation in human T24 bladder cancer cells

Phytomedicine. 2010 Apr;17(5):363-8. doi: 10.1016/j.phymed.2009.07.019. Epub 2009 Sep 11.

Abstract

It is well known that the garlic-derived organosulfur compounds (OSCs) are effective to inhibit a variety of human cancers such as prostate, breast, colon, skin, lung, and bladder cancers. Herein, the pro-apoptotic effects of diallyl trisulfide (DATS), one of garlic-derived OSCs, on T24 bladder cancer cells were investigated. The results demonstrated that DATS suppressed proliferation of T24 bladder cancer cells in a dose- and time-dependent manner which was associated with induced G2/M Phase cell cycle arrest and apoptosis. Mechanistically, DATS inhibits phosphatidylinositol 3'-kinase/Akt activation that, in turn, results in modulation of Bcl-2 family proteins, leading to enhanced apoptosis of T24 cells. These findings suggest that DATS may be an effective way for treating human bladder and other types of cancers.

MeSH terms

  • Allyl Compounds / pharmacology
  • Allyl Compounds / therapeutic use*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Garlic / chemistry*
  • Humans
  • Phosphorylation / drug effects
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Protein Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Sulfides / pharmacology
  • Sulfides / therapeutic use*
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / metabolism

Substances

  • Allyl Compounds
  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • Sulfides
  • diallyl trisulfide
  • Protein Kinases
  • Proto-Oncogene Proteins c-akt
  • Caspase 3