Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.61 (caspase-8)
 6,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Light-activated indole-3-acetic acid induces apoptosis in g361 human melanoma cells. 1714 72

Indole-3-acetic acid (IAA) and horseradish peroxidase (HRP) have emerged as a new strategy for cancer treatment. In the present study, we determined the effects of IAA/HRP treatment on TCCSUP human urinary bladder carcinoma cells. It was found that the IAA/HRP combination decreased cell viability of TCCSUP cells in a time- and dose-dependent manner, whereas IAA or HRP alone showed no such effect. In addition, the decreased cell viability was restored by pretreatment with ascorbic acid. To clarify the mechanism of death of TCCSUP cells by IAA/HRP, we investigated the signal transduction pathways related to the apoptosis. It was found that IAA/HRP activates p38 mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK). We further investigated the IAA/HRP-mediated apoptotic pathways and showed that IAA/HRP induces caspase-8 and caspase-9 activation, which results in caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage. To further confirm whether IAA/HRP induces apoptotic cell death, we performed a DNA fragmentation assay after IAA/HRP treatment and found that IAA/HRP-treated cells showed typical apoptotic DNA ladder formation. From these results, we suggest that IAA/HRP induces apoptosis of TCCSUP human urinary bladder carcinoma cells via both death receptor-mediated and mitochondrial apoptotic pathways.
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PMID:Indole-3-acetic acid/horseradish peroxidase induces apoptosis in TCCSUP human urinary bladder carcinoma cells. 2022 57