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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MDPI AG
2020-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/9/1976 |
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| author | Santosh Kumar Singh Jennifer B. Gordetsky Sejong Bae Edward P. Acosta James W. Lillard Rajesh Singh |
| author_facet | Santosh Kumar Singh Jennifer B. Gordetsky Sejong Bae Edward P. Acosta James W. Lillard Rajesh Singh |
| author_sort | Santosh Kumar Singh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T16:45:40Z |
| format | Article |
| id | doaj.art-3fb34d388eef48e98475b8c555f3fc45 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T16:45:40Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-3fb34d388eef48e98475b8c555f3fc452023-11-20T11:35:41ZengMDPI AGCells2073-44092020-08-0199197610.3390/cells9091976Selective Targeting of the Hedgehog Signaling Pathway by PBM Nanoparticles in Docetaxel-Resistant Prostate CancerSantosh Kumar Singh0Jennifer B. Gordetsky1Sejong Bae2Edward P. Acosta3James W. Lillard4Rajesh Singh5Department of Microbiology, Biochemistry and Immunology, Cancer Health Equity Institute, Morehouse School of Medicine, Atlanta, GA 30310, USADepartments of Pathology and Urology, Vanderbilt University Medical Center, Nashville, TN 37232, USADivision of Preventive Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35205, USADepartment of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USADepartment of Microbiology, Biochemistry and Immunology, Cancer Health Equity Institute, Morehouse School of Medicine, Atlanta, GA 30310, USADepartment of Microbiology, Biochemistry and Immunology, Cancer Health Equity Institute, Morehouse School of Medicine, Atlanta, GA 30310, USAAn 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.https://www.mdpi.com/2073-4409/9/9/1976prostate cancerthymoquinonedrug transporternanoparticlesaptamer |
| spellingShingle | Santosh Kumar Singh Jennifer B. Gordetsky Sejong Bae Edward P. Acosta James W. Lillard Rajesh Singh Selective Targeting of the Hedgehog Signaling Pathway by PBM Nanoparticles in Docetaxel-Resistant Prostate Cancer Cells prostate cancer thymoquinone drug transporter nanoparticles aptamer |
| title | Selective Targeting of the Hedgehog Signaling Pathway by PBM Nanoparticles in Docetaxel-Resistant Prostate Cancer |
| title_full | Selective Targeting of the Hedgehog Signaling Pathway by PBM Nanoparticles in Docetaxel-Resistant Prostate Cancer |
| title_fullStr | Selective Targeting of the Hedgehog Signaling Pathway by PBM Nanoparticles in Docetaxel-Resistant Prostate Cancer |
| title_full_unstemmed | Selective Targeting of the Hedgehog Signaling Pathway by PBM Nanoparticles in Docetaxel-Resistant Prostate Cancer |
| title_short | Selective Targeting of the Hedgehog Signaling Pathway by PBM Nanoparticles in Docetaxel-Resistant Prostate Cancer |
| title_sort | selective targeting of the hedgehog signaling pathway by pbm nanoparticles in docetaxel resistant prostate cancer |
| topic | prostate cancer thymoquinone drug transporter nanoparticles aptamer |
| url | https://www.mdpi.com/2073-4409/9/9/1976 |
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