Indole-3-acetic acid/horseradish peroxidase induces apoptosis in TCCSUP human urinary bladder carcinoma cells.
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.
Department of Biochemistry, College of Medicine, Chung-Ang University, Dongjak-gu, Seoul, Korea.
Yun-Mi
YM
Jeong
Mi Hee
MH
Oh
Su Yeon
SY
Kim
Hailan
H
Li
Hye-Young
HY
Yun
Kwang Jin
KJ
Baek
Nyoun Soo
NS
Kwon
Won Yong
WY
Kim
Dong-Seok
DS
Kim
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D005840:Gentian Violet; D006360:Heat-Shock Proteins / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000494:pharmacology*; D006801:Humans; D007210:Indoleacetic Acids / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
D006360:Heat-Shock Proteins; D007210:Indoleacetic Acids; C030737:indoleacetic acid; D006735:Horseradish Peroxidase; D005840:Gentian Violet