Diallyl disulfide causes caspase-dependent apoptosis in human cancer cells through a Bax-triggered mitochondrial pathway

J Nutr Biochem. 2010 May;21(5):405-12. doi: 10.1016/j.jnutbio.2009.01.015. Epub 2009 May 7.


Diallyl disulfide (DADS), an important component of garlic (Allium sativum) derivative, has been demonstrated to exert a potential molecular target against human cancers. We investigated DADS-induced expressions of Apaf1, cystatin B, caspase-3 and FADD (fas-associated protein with death domain) in breast, prostate and lung cancer cells. These showed coincident data when further examined by quantitative reverse transcription-polymerase chain reaction and Western blot analysis. Furthermore, DADS induced a marked amount of Bax translocation, cytochrome c release and activation of caspase-3 and caspase-9. DADS-treated tumor cells triggered mitochondria-mediated signaling pathways that led to a significant increase in apoptosis induction. Further studies with caspase-3 and caspase-9 inhibitors (zDEVD-fmk and zLEHD-fmk, respectively) proved that DADS induces apoptosis through a caspase-3-dependent pathway. DADS is only an agent used in the study. The molecular mechanism presented therefore provides strong additional support to the hypothesis that DADS is a strong inducer of apoptosis through a Bax-triggered mitochondria-mediated and caspase-3-dependent pathway. This study shows clearly that DADS causes caspase-dependent apoptosis in human cancer cells through a Bax-triggered mitochondrial pathway. Therefore, the mitochondrial pathway might be the target for cancer chemoprevention and/or chemotherapy by DADS.

Publication types

  • Comparative Study

MeSH terms

  • Allyl Compounds / pharmacology*
  • Anticarcinogenic Agents / pharmacology
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Apoptotic Protease-Activating Factor 1 / genetics
  • Apoptotic Protease-Activating Factor 1 / metabolism
  • Caspase 3 / genetics
  • Caspase 3 / metabolism*
  • Caspase 9 / metabolism
  • Caspase Inhibitors
  • Cell Line, Tumor
  • Chemoprevention
  • Cystatin B / genetics
  • Cystatin B / metabolism
  • Cytochromes c / metabolism
  • Disulfides / pharmacology*
  • Fas-Associated Death Domain Protein / genetics
  • Fas-Associated Death Domain Protein / metabolism
  • Garlic / chemistry
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mitochondria / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Neoplasms / prevention & control
  • Plant Roots / chemistry
  • Protein Transport / drug effects
  • Signal Transduction / drug effects*
  • bcl-2-Associated X Protein / metabolism*


  • APAF1 protein, human
  • Allyl Compounds
  • Anticarcinogenic Agents
  • Antineoplastic Agents, Phytogenic
  • Apoptotic Protease-Activating Factor 1
  • BAX protein, human
  • CSTB protein, human
  • Caspase Inhibitors
  • Disulfides
  • FADD protein, human
  • Fas-Associated Death Domain Protein
  • bcl-2-Associated X Protein
  • diallyl disulfide
  • Cystatin B
  • Cytochromes c
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9