Se-Methyl-L-selenocysteine Induces Apoptosis via Endoplasmic Reticulum Stress and the Death Receptor Pathway in Human Colon Adenocarcinoma COLO 205 Cells.

Abstract

Selenomethionine (SeMet) and Se-methyl-L-selenocysteine (MSeC) are natural organoselenium compounds found in garlic, onion, and broccoli. In addition, these compounds have lower toxicity and better anticancer activities than inorganic Se. This study investigated the effects of MSeC treatment on the growth of COLO 205 human colorectal adenocarcinoma cells and evaluated the mechanisms related to the MSeC-induced effects. When COLO 205 cells were treated with 200 μM MSeC for 24 h, MSeC caused 80% apoptosis in cells. MSeC increased the expression of Fas and FasL, followed by the cleavage of caspase-3, caspase-8, DNA fragmentation factor (DFF45), and poly(ADP-ribose) polymerase (PARP). MSeC also increased the levels of Bax protein and decreased the levels of Bid and Bcl-2 proteins. However, MSeC did not cause apoptosis through reactive oxygen species (ROS) stress but instead through endoplasmic reticulum (ER) stress. The cleavage of caspase-12 and caspase-9 was shown to increase the growth arrest and protein levels of DNA-damage inducible genes (GADD) 153 and 45. MSeC also downregulated the ERK1/2 and PI3K/AKT protein levels and upregulated the p38 and JNK protein levels in COLO 205 cells. These results showed that the mechanism by which MSeC induced apoptosis in COLO 205 cells involved caspase activation, the extrinsic apoptotic pathway, and the regulation of ER-stress-induced apoptosis.

• Authors: Yen-Chen Tung, Mei-Ling Tsai, Fang-Ling Kuo, Ching-Shu Lai, Vladimir Badmaev, Chi-Tang Ho, Min-Hsiung Pan
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 63 Issue 20 Pg. 5008-16 (May 27 2015) ISSN: 1520-5118 [Electronic] United States
• PMID: 25943382 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• DDIT3 protein, human
• caspase-activated DNase inhibitor
• Selenocysteine
• Transcription Factor CHOP
• Poly(ADP-ribose) Polymerases
• Caspase 3
• Caspase 8
• Caspase 9
• selenomethylselenocysteine

Topics

• Adenocarcinoma (drug therapy, physiopathology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Caspase 3 (genetics, metabolism)
• Caspase 8 (genetics, metabolism)
• Caspase 9 (genetics, metabolism)
• Cell Line, Tumor
• Colonic Neoplasms (drug therapy, physiopathology)
• Endoplasmic Reticulum Stress (drug effects)
• Humans
• Poly(ADP-ribose) Polymerases (genetics, metabolism)
• Selenocysteine (analogs & derivatives, pharmacology)
• Transcription Factor CHOP (genetics, metabolism)