Back to Search
Start Over
Inhibition of autophagy prevents cadmium-induced prostate carcinogenesis
- Source :
- British Journal of Cancer
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Background: Cadmium, an established carcinogen, is a risk factor for prostate cancer. Induction of autophagy is a prerequisite for cadmium-induced transformation and metastasis. The ability of Psoralidin (Pso), a non-toxic, orally bioavailable compound to inhibit cadmium-induced autophagy to prevent prostate cancer was investigated. Methods: Psoralidin was studied using cadmium-transformed prostate epithelial cells (CTPE), which exhibit high proliferative, invasive and colony forming abilities. Gene and protein expression were evaluated by qPCR, western blot, immunohistochemistry and immunofluorescence. Xenograft models were used to study the chemopreventive effects in vivo. Results: Cadmium-transformed prostate epithelial cells were treated with Pso resulting in growth inhibition, without causing toxicity to normal prostate epithelial cells (RWPE-1). Psoralidin-treatment of CTPE cells inhibited the expression of Placenta Specific 8, a lysosomal protein essential for autophagosome and autolysosome fusion, which resulted in growth inhibition. Additionally, Pso treatment caused decreased expression of pro-survival signalling proteins, NFκB and Bcl2, and increased expression of apoptotic genes. In vivo, Pso effectively suppressed CTPE xenografts growth, without any observable toxicity. Tumours from Pso-treated animals showed decreased autophagic morphology, mesenchymal markers expression and increased epithelial protein expression. Conclusions: These results confirm that inhibition of autophagy by Pso plays an important role in the chemoprevention of cadmium-induced prostate carcinogenesis.
- Subjects :
- Male
0301 basic medicine
Cancer Research
Pathology
Carcinogenesis
Autolysosome
Fluorescent Antibody Technique
Apoptosis
medicine.disease_cause
Polymerase Chain Reaction
Psoralidin
Prostate cancer
chemistry.chemical_compound
Coumarins
Prostate
chemoprevention
Cells, Cultured
Chemistry
NF-kappa B
prostate cancer
Immunohistochemistry
medicine.anatomical_structure
Proto-Oncogene Proteins c-bcl-2
Oncology
Growth inhibition
Cadmium
autophagy
medicine.medical_specialty
Blotting, Western
Mice, Nude
03 medical and health sciences
In Situ Nick-End Labeling
medicine
Animals
Humans
Benzofurans
Cell Proliferation
Cell growth
Autophagy
Autophagosomes
Prostatic Neoplasms
Proteins
medicine.disease
030104 developmental biology
Cancer research
Lysosomes
Translational Therapeutics
Neoplasm Transplantation
Subjects
Details
- ISSN :
- 15321827 and 00070920
- Volume :
- 117
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....949c044cc9e90262bf1a5091c6d334d0