Light-activated indole-3-acetic acid induces apoptosis in g361 human melanoma cells.
Indole-3-acetic acid (IAA) activation by horseradish peroxidase (HRP) has been suggested as a new cancer therapy. Interestingly, we found that ultraviolet B UVB radiation also can activate IAA and produce free radicals in a dose-dependent manner. In this study, we attempted to identify the free radicals generated by UVB-irradiated IAA (IAAUVB), and to determine whether IAAUVB can induce the apoptosis of G361 human melanoma cells. Since IAA/HRP produces reactive oxygen species (ROS), we examined whether IAAUVB-generated radicals include ROS. Our results show that IAAUVB-induced free radical production is not inhibited by catalase, superoxide dismutase, or sodium formate, indicating that ROS are not generated by IAAUVB. On the other hand, IAAUVB caused lipid peroxidation, and this was blocked by Trolox, a water-soluble vitamin E derivative. Moreover, we found that IAAUVB caused apoptotic cell death and that this was inhibited by a low temperature. We further investigated IAAUVB-mediated apoptotic pathways, and found that IAAUVB causes caspase-8, Bid, caspase-3 activation, and poly (ADP-ribose) polymerase (PARP) cleavage. In addition, these apoptotic pathways were also blocked by low temperature. From these results, we propose that IAAUVB-induced free radicals cause human melanoma cell apoptosis via a death receptor-mediated apoptotic pathway.
Kim
Dong-Seok
DS
Department of Dermatology, Seoul National University College of Medicine, Korea.
Kim
So-Young
SY
Jeong
Yun-Mi
YM
Jeon
Sang-Eun
SE
Kim
Myo-Kyoung
MK
Kwon
Sun-Bang
SB
Na
Jung-Im
JI
Park
Kyoung-Chan
KC
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003080:Cold Temperature; D005434:Flow Cytometry; D006801:Humans; D007210:Indoleacetic Acids / Q000494:pharmacology*; D008027:Light; D015227:Lipid Peroxidation; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D007210:Indoleacetic Acids; D017382:Reactive Oxygen Species; C030737:indoleacetic acid