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Diallyl trisulfide induces apoptosis in human primary colorectal cancer cells.

Abstract
Colorectal cancer (CRC) is one of the most prevalent types of cancer worldwide and a common cause of morbidity and mortality in humans. The garlic-derived organosulfur compound diallyl trisulfide (DATS) has been shown to induce apoptosis in many human cancer cell lines in vitro and also affords significant protection against cancer in animal tumor models in vivo. There is no available information to show DATS-induced apoptosis in vitro and the molecular mechanisms of apoptosis in human primary colorectal cancer cells. In this study, we investigated the cytotoxic effects in DATS in primary colorectal cancer cells. DATS inhibited the viability of primary colorectal cancer cells in a time- and dose-dependent manner. After treatment with DATS, primary colorectal cancer cells exhibited DNA condensation by DAPI stain. DATS increased reactive oxygen species (ROS) production in primary colorectal cancer cells. The mitochondria-dependent apoptotic signaling pathway was shown to be involved as determined by increase in the levels of cytochrome c, Apaf-1, AIF and caspase-3 and caspase-9 in DATS-treated primary colorectal cancer cells. The decrease in the level of ΔΨm was associated with an increase in the Bax/Bcl-2 ratio which led to activation of caspase-9 and -3. Based on our results, DATS induces apoptotic cell death in human primary colorectal cancer cells through a mitochondria-dependent signaling pathway.
AuthorsChun-Shu Yu, An-Cheng Huang, Kuang-Chi Lai, Yi-Ping Huang, Meng-Wei Lin, Jai-Sing Yang, Jing-Gung Chung
JournalOncology reports (Oncol Rep) Vol. 28 Issue 3 Pg. 949-54 (Sep 2012) ISSN: 1791-2431 [Electronic] Greece
PMID22736270 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Allyl Compounds
  • Antineoplastic Agents
  • Reactive Oxygen Species
  • Sulfides
  • diallyl trisulfide
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9
Topics
  • Allyl Compounds (pharmacology)
  • Antineoplastic Agents (pharmacology)
  • Apoptosis (drug effects)
  • Caspase 3 (metabolism)
  • Caspase 9 (metabolism)
  • Cell Survival (drug effects)
  • Colorectal Neoplasms (drug therapy, pathology)
  • Drug Screening Assays, Antitumor
  • Humans
  • Membrane Potential, Mitochondrial (drug effects)
  • Primary Cell Culture
  • Reactive Oxygen Species (metabolism)
  • Sulfides (pharmacology)
  • Tumor Cells, Cultured (drug effects)

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