@article { author = {Onishi, Kenta and Miyake, Makito and Tatsumi, Yoshihiro and Hori, Shunta and Nakai, Yasushi and Onishi, Sayuri and Iemura, Yusuke and Owari, Takuya and Itami, Yoshitaka and Iida, Kota and Anai, Satoshi and Tanaka, Nobumichi and Shimada, Keiji and Fujimoto, Kiyohide}, title = {Inhibitory Effect of Orally Administered 5-Aminolevulinic Acid on Prostate Carcinogenesis in the FVB-Transgenic Adenocarcinoma of a Mouse Prostate (FVB-TRAMP) Model}, journal = {Asian Pacific Journal of Cancer Prevention}, volume = {21}, number = {12}, pages = {3743-3749}, year = {2020}, publisher = {West Asia Organization for Cancer Prevention (WAOCP), APOCP's West Asia Chapter.}, issn = {1513-7368}, eissn = {2476-762X}, doi = {10.31557/APJCP.2020.21.12.3743}, abstract = {Background: 5-aminolevulinic acid (5-ALA) is a constituent of mitochondrial electron carriers, heme and cytochrome c, which are crucial for aerobic energy metabolism and cell apoptosis. We investigated the chemopreventive efficacy of 5-ALA against prostate cancer using the FVB-transgenic adenocarcinoma of mouse prostate (FVB-TRAMP) model. Methods: Samples were collected from 24 FVB-TRAMP mice at 12 and 20 weeks of age (named the first and second sets, respectively). Sixteen mice (from the first set) were randomly allocated into 3 treatment groups: 1) control (no treatment), 2) low dose of 5-ALA (30 mg/kg/day), and 3) high dose of 5-ALA (300 mg/kg/day). Similarly, 8 mice were divided into 2 treatment groups: 1) control and 2) high dose of 5-ALA (300 mg/kg/day). 5-ALA was orally administered to mice before cancer onset, from 6 weeks of age. Results: In the control group, prostate cancer was pathologically detected in 33 and 50 % of mice at 12 and 20 weeks, respectively, while 25% of 12-week old mice in the low-dose group were affected and none of the high-dose group mice developed prostate cancer. Immunohistochemical analysis showed higher expression of cytochrome c oxidase subunit 4 (COX4) in the prostate gland of the high-dose group compared to the control (P = 0.018). Similarly, enzyme-linked immunosorbent assay using lysed prostate tissue revealed higher amounts of cytochrome c in the prostate of the high-dose group compared to the control (P = 0.021). Furthermore, western blot analysis showed higher level of cleaved caspase-3 in mice in the high-dose group diagnosed with high-grade prostatic intraepithelial neoplasia. Conclusion: Our results suggest that oral 5-ALA may support the functional expression of mitochondrial cytochrome c and COX4, leading to caspase 3-dependent apoptosis in carcinogenesis in FVB-TRAMP mice. Future clinical studies are warranted to confirm the chemopreventive value of 5-ALA in prostate carcinogenesis.   }, keywords = {Prostate Cancer,5-aminolevulic acid,Chemoprevention,Apoptosis,FVB-TRAMP}, url = {https://journal.waocp.org/article_89410.html}, eprint = {https://journal.waocp.org/article_89410_6b77ea8b3eb5a48de1fa02c2bbfc3145.pdf} }