Molecular mechanism of diallyl disulfide in cell cycle arrest and apoptosis in HCT-116 colon cancer cells

• Published in: Journal of biochemical and molecular toxicology 2009-01, Vol.23 (1), p.71-79
• Main Authors: Song, Ju-Dong, Lee, Sang Kwon, Kim, Kang Mi, Park, Si Eun, Park, Sung-Joo, Kim, Koan Hoi, Ahn, Soon Cheol, Park, Young Chul
• Format: Article
• Language: English
• Subjects: Allium sativum; Allyl Compounds - pharmacology; Antioxidants - metabolism; Apoptosis; Apoptosis - drug effects; CDC2 Protein Kinase - metabolism; Cell Cycle - drug effects; Cell Cycle Arrest; Cell Proliferation - drug effects; Cell Survival - drug effects; Colonic Neoplasms - pathology; Cyclin B - metabolism; Cyclin B1; Dially Disulfide; Disulfides - pharmacology; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Flow Cytometry; HCT116 Cells; Humans; Oligomycin; Oligomycins - pharmacology; p53; Poly(ADP-ribose) Polymerases - metabolism; Reactive Oxygen Species; Reactive Oxygen Species - metabolism; RNA, Small Interfering - metabolism; Time Factors; Tumor Suppressor Protein p53 - metabolism
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.20266

Diallyl disulfide (DADS) is the most prevalent oil‐soluble sulfur compound in garlic and inhibits cell proliferation in many cancer cell lines. Here we examined DADS cytotoxicity in a redox‐mediated process, involving reactive oxygen species (ROS) production. In the present study, p53‐independent cell cycle arrest at G2/M phase was observed with DADS treatment, along with time‐dependent increase of cyclin B1. In addition, apoptosis was also observed upon 24‐h DADS treatment accompanied by activation of p53. In HCT‐116 cells, DADS application induced a dose‐dependent increase and time‐dependent changes in ROS production. Scavenging of DADS‐induced ROS by N‐acetyl cysteine or reduced glutathione inhibited cell cycle arrest, apoptosis and p53 activation by DADS. These results suggest that ROS trigger the DADS‐induced cell cycle arrest and apoptosis and that ROS are involved in stress‐induced signaling upstream of p53 activation. Transfection of p53 small interfering RNA prevents the accumulation of cleaved poly(ADP‐ribose) polymerase and sub‐G1 cell population by 65% and 35%, respectively. Moreover, DADS‐induced apoptosis was also prevented by treatment with oligomycin, which is known to prevent p53‐dependent apoptosis by reducing ROS levels in mitochondria. These results suggest that mitochondrial ROS may serve as second messengers in DADS‐induced apoptosis, which requires activation of p53. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:71–79, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20266