Abstract
5-Hydroxyindole-3-acetic acid (5-HIAA), an indole derivative, is the main metabolite of serotonin in the human body. We determined whether or not ultraviolet B (UVB)-activated 5-HIAA (5-HIAA UVB) affects the viability of human prostate (LnCaP and PC-3) and bladder cancer cells (TCCSUP). While 5-HIAA alone had no cytotoxic effect at <1 mM, 5-HIAA UVB induced LnCaP, PC-3, and TCCSUP cell death in a time- and dose-dependent manner. Cell cycle analysis showed that 5-HIAA UVB markedly increased the sub-G 0/G 1 phase and resulted in cell cycle disruption. To elucidate the death mechanism by 5-HIAA UVB, we examined the signal transduction pathways related to apoptosis using Western blot analysis. 5-HIAA UVB led to phosphorylation of stress-activated signaling proteins, such as c-Jun N-terminal kinase (JNK) and/or p38 mitogen-activated protein kinase (MAPK). Furthermore, 5-HIAA UVB activated caspase-8, -9, and -3 and cleaved poly(ADP-ribose) polymerase (PARP), which are indicators of apoptosis. From these findings, the present study demonstrated that 5-HIAA UVB induces apoptotic cell death of prostate and bladder cancer cells via stress-mediated signaling and apoptotic pathways. Therefore, we suggest that 5-HIAA might be used as a new photosensitizer for photodynamic cancer therapy.
Published Version
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