Diallyl trisulfide induces apoptosis in human primary colorectal cancer             cells.
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.
School of Pharmacy, Department of Physiology, China Medical University, Taichung 404, Taiwan, ROC.
Chun-Shu
CS
Yu
An-Cheng
AC
Huang
Kuang-Chi
KC
Lai
Yi-Ping
YP
Huang
Meng-Wei
MW
Lin
Jai-Sing
JS
Yang
Jing-Gung
JG
Chung
D000498:Allyl Compounds / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D061251:Primary Cell Culture; D017382:Reactive Oxygen Species / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000498:Allyl Compounds; D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D013440:Sulfides; C042577:diallyl trisulfide; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9