Inhibitory Effect of Orally Administered 5-Aminolevulinic Acid on Prostate Carcinogenesis in the FVB-Transgenic Adenocarcinoma of a Mouse Prostate (FVB-TRAMP) Model.
5-aminolevulic acid
Apoptosis
Chemoprevention
FVB-TRAMP
Prostate Cancer
Journal
Asian Pacific journal of cancer prevention : APJCP
ISSN: 2476-762X
Titre abrégé: Asian Pac J Cancer Prev
Pays: Thailand
ID NLM: 101130625
Informations de publication
Date de publication:
01 Dec 2020
01 Dec 2020
Historique:
received:
21
07
2020
entrez:
28
12
2020
pubmed:
29
12
2020
medline:
2
9
2021
Statut:
epublish
Résumé
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. 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. 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. 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. <br />.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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. <br />.
Identifiants
pubmed: 33369476
doi: 10.31557/APJCP.2020.21.12.3743
pmc: PMC8046295
pii:
doi:
Substances chimiques
Photosensitizing Agents
0
Aminolevulinic Acid
88755TAZ87
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3743-3749Références
PLoS One. 2013 Dec 06;8(12):e80850
pubmed: 24324635
Am J Pathol. 2008 Jan;172(1):236-46
pubmed: 18156212
Asian Pac J Cancer Prev. 2011;12(12):3331-4
pubmed: 22471475
Oncol Rep. 2014 Mar;31(3):1282-6
pubmed: 24366173
Oncotarget. 2016 Aug 16;7(33):53751-53761
pubmed: 27447565
Cancer Res. 2004 Dec 1;64(23):8715-22
pubmed: 15574782
Curr Dev Nutr. 2017 Dec 26;2(3):nzy002
pubmed: 30019025
Prostate. 2019 Mar;79(4):340-351
pubmed: 30450646
Mol Med Rep. 2015 Mar;11(3):1813-9
pubmed: 25420581
Int Immunopharmacol. 2011 Mar;11(3):358-65
pubmed: 21144919
Oxid Med Cell Longev. 2015;2015:938475
pubmed: 26180600
BMC Res Notes. 2011 Mar 17;4:66
pubmed: 21414200
Cancer Res. 2001 Sep 15;61(18):6777-82
pubmed: 11559550
Oncotarget. 2018 Apr 13;9(28):19508-19524
pubmed: 29731962
Int J Cancer. 2004 Dec 10;112(5):823-9
pubmed: 15386368
Antioxid Redox Signal. 2007 Dec;9(12):2099-117
pubmed: 17822372
J Carcinog. 2007 Mar 16;6:3
pubmed: 17367528
Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3439-43
pubmed: 7724580
Anticancer Res. 2013 Jul;33(7):2957-63
pubmed: 23780986
Cancer Sci. 2014 May;105(5):616-22
pubmed: 24602011
Arch Biochem Biophys. 1990 Aug 1;280(2):252-62
pubmed: 2164355
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
BMC Pharmacol Toxicol. 2015 Dec 15;16:41
pubmed: 26670903
J Pathol. 2013 Dec;231(4):495-504
pubmed: 24549646
Cancer. 1997 Jun 15;79(12):2282-308
pubmed: 9191516