Selective Targeting of the Hedgehog Signaling Pathway by PBM Nanoparticles in Docetaxel-Resistant Prostate Cancer

An abnormality in hedgehog (Hh) signaling has been implicated in the progression of prostate cancer (PCa) to a more aggressive and therapy-resistant disease. Our assessments of human PCa tissues have shown an overexpression of the Hh pathway molecules, glioma-associated oncogene homolog 1 (GLI-1), a...

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Published in:Cells (Basel, Switzerland) Switzerland), 2020-08, Vol.9 (9), p.1976
Main Authors: Singh, Santosh Kumar, Gordetsky, Jennifer B, Bae, Sejong, Acosta, Edward P, Lillard, Jr, James W, Singh, Rajesh
Format: Article
Language:English
Subjects:
aptamer
Aptamers
Cancer therapies
Cell Proliferation
Drug resistance
Drug Resistance, Neoplasm - drug effects
drug transporter
Drugs
Glioma
Health aspects
Hedgehog protein
Hedgehog proteins
Hedgehog Proteins - metabolism
Humans
Male
Metastasis
Nanoparticles
Nanoparticles - metabolism
Particle size
Physiological aspects
Polyethylene glycol
Polysaccharides
Prostate cancer
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
Ribonucleic acid
RNA
Sensors
Signal Transduction
thymoquinone
Tumors
Zirconium oxides
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Summary:An abnormality in hedgehog (Hh) signaling has been implicated in the progression of prostate cancer (PCa) to a more aggressive and therapy-resistant disease. Our assessments of human PCa tissues have shown an overexpression of the Hh pathway molecules, glioma-associated oncogene homolog 1 (GLI-1), and sonic hedgehog (SHH). The effect of the natural compound thymoquinone (TQ) in controlling the expression of Hh signaling molecules in PCa was investigated in this study. We generated planetary ball-milled nanoparticles (PBM-NPs) made with a natural polysaccharide, containing TQ, and coated with an RNA aptamer, A10, which binds to prostate-specific membrane antigen (PSMA). We prepared docetaxel-resistant C4-2B-R and LNCaP-R cells with a high expression of Hh, showing the integration of drug resistance and Hh signaling. Compared to free TQ, A10-TQ-PBM-NPs were more effective in controlling the Hh pathway. Our findings reveal an effective treatment strategy to inhibit the Hh signaling pathway, thereby suppressing PCa progression.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells9091976