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

Nagaraj Nagathihalli, Kandangath R. Anilakumar, Om V. Singh

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)405-412
Number of pages8
JournalJournal of Nutritional Biochemistry
Volume21
Issue number5
DOIs
StatePublished - May 2010
Externally publishedYes

Fingerprint

Caspases
Cells
Apoptosis
Caspase 3
Neoplasms
Garlic
Mitochondria
Caspase 9
Cystatin B
Fas-Associated Death Domain Protein
diallyl disulfide
Caspase Inhibitors
Chemotherapy
Polymerase chain reaction
Chemoprevention
Transcription
Cytochromes c
Reverse Transcription
Tumors
Lung Neoplasms

Keywords

  • Apoptosis
  • Caspase-3
  • Diallyl disulfide
  • Garlic
  • Mitochondria
  • Tumor

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Diallyl disulfide causes caspase-dependent apoptosis in human cancer cells through a Bax-triggered mitochondrial pathway. / Nagathihalli, Nagaraj; Anilakumar, Kandangath R.; Singh, Om V.

In: Journal of Nutritional Biochemistry, Vol. 21, No. 5, 05.2010, p. 405-412.

Research output: Contribution to journalArticle

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