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.
Highlights
Prostate cancer is one of the most common malignant diseases in men and is a major cause of mortality
This study focused on the potential of 5-aminolevulinic acid (5-ALA) as a chemopreventive agent using the FVB-transgenic adenocarcinoma of mouse prostate (TRAMP) model. 5-ALA is a naturally occurring amino acid found in plants and animals, and represents the first product of the porphyrin synthetic pathway with heme and cytochrome as the final products (Peng et al, 1997). 5-ALA plays an
We investigated whether orally administered 5-ALA has inhibitory effects on the carcinogenesis and progression of prostate cancer in an FVB-TRAMP model
Summary
Prostate cancer is one of the most common malignant diseases in men and is a major cause of mortality. Almost 1.3 million new cases of prostate cancer and 359,000 prostate cancer-associated deaths worldwide have occurred in 2018 (Bray et al, 2018). Patients in the early stage of prostate cancer can opt for any treatment option, and many of them are cured. Once a patient reaches the castration-resistant state of the disease, no curative treatment option is available. Much attention has been paid to agents useful in preventive strategies against prostate carcinogenesis. The transgenic adenocarcinoma of mouse prostate (TRAMP) model of prostate cancer was utilized to examine the chemopreventive effect of these agents since these tumors occur in the prostate epithelium and the histopathology of the tumor tissue closely mimics human prostate cancer
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