Indole-3-Acetic Acid/Horseradish Peroxidase-Induced Apoptosis Involves Cell Surface CD95 (Fas/APO-1) Expression

• Published in: Biological & Pharmaceutical Bulletin Vol. 29; no. 8; pp. 1625 - 1629
• Main Authors: Kim, Dong-Seok, Kim, So-Young, Jeong, Yun-Mi, Jeon, Sang-Eun, Kim, Myo-Kyoung, Kwon, Sun-Bang, Park, Kyoung-Chan
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.08.2006; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Antibodies - immunology; apoptosis; Apoptosis - drug effects; Blotting, Western; Catalase - metabolism; CD95 (Fas/APO-1); Cell Line, Tumor; Cell Membrane - metabolism; fas Receptor - immunology; fas Receptor - metabolism; Flow Cytometry; horseradish peroxidase; Horseradish Peroxidase - pharmacology; Humans; indole-3-acetic acid; Indoleacetic Acids - pharmacology; melanoma; Microscopy, Confocal
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.29.1625

Recently, we showed that a combination of indole-3-acetic acid (IAA) and horseradish peroxidase (HRP) produces hydrogen peroxide (H2O2), and that this leads to the apoptosis of G361 human melanoma cells. In the present study, flow cytometric analysis confirmed that H2O2 is involved the IAA/HRP-induced apoptotic process. We also found that IAA/HRP increases cell surface CD95 (Fas/APO-1) expression, and that this is blocked by catalase treatment. Furthermore, blocking CD95 with a neutralizing antibody significantly restored IAA/HRP-induced apoptosis. In addition, the IAA/HRP-induced activations of CD95 downstream molecules, i.e., caspase-8, Bid, and caspase-3, were also inhibited by catalase. Moreover, a caspase-8 inhibitor significantly blocked IAA/HRP-induced apoptosis. These results indicate that IAA/HRP-induced apoptosis involves a CD95-initiated death receptor signaling pathway initiated by hydrogen peroxide.