title: Photo-activated 5-hydroxyindole-3-acetic acid induces apoptosis of prostate and bladder cancer cells.
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 <1mM, 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.
authors.affiliation: Department of Biochemistry, Chung-Ang University College of Medicine, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors.forename: Yun-Mi
authors.initials: YM
authors.lastname: Jeong
authors.forename: Hailan
authors.initials: H
authors.lastname: Li
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Woo-Jae
authors.initials: WJ
authors.lastname: Park
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Yun
authors.forename: Kwang Jin
authors.initials: KJ
authors.lastname: Baek
authors.forename: Nyoun Soo
authors.initials: NS
authors.lastname: Kwon
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Soon Chul
authors.initials: SC
authors.lastname: Myung
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D045744:Cell Line, Tumor; D016193:G1 Phase / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008027:Light; D008297:Male; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
chemical_list: D007211:Indoles; D017319:Photosensitizing Agents; C018079:5-(hydroxy-3-indolyl)lactic acid