Active Targeting of P-Selectin by Fucoidan Modulates the Molecular Profiling of Metastasis in Docetaxel-Resistant Prostate Cancer

The standard of care for prostate cancer (PCa) is androgen deprivation therapy (ADT). Although hormone-sensitive PCa is curable by ADT, most conditions progress to castration-resistant prostate cancer (CRPCa) and metastatic CRPCa (mCRPCa). Front-line docetaxel has been administered to patients with...

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Bibliographic Details
Published in:Marine drugs 2022-08, Vol.20 (9), p.542
Main Authors: Ho, Chang-Hsun, Chen, Mei-Lin, Huang, Hau-Lun, Lai, Chih-Jen, Liu, Chih-Hsin, Chuu, Chih-Pin, Lin, Yu-Hsin
Format: Article
Language:English
Subjects:
ABC transporters
Androgens
Anticancer properties
Biological activity
Cancer
Cancer therapies
Castration
Cell migration
Cells
Chemotherapy
Combined treatment
Cyclooxygenase-2
Deprivation
docetaxel resistant
Drug resistance
Endothelium
Fucoidan
Hormones
Interleukin 1 receptors
Ligands
Metastases
Metastasis
metastasis-inhibiting signaling pathway
Motility
NF-κB protein
P-selectin
Patients
Prostate cancer
Protein expression
Proteins
Signal transduction
Synergistic effect
synergistic effects
Tumors
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Summary:The standard of care for prostate cancer (PCa) is androgen deprivation therapy (ADT). Although hormone-sensitive PCa is curable by ADT, most conditions progress to castration-resistant prostate cancer (CRPCa) and metastatic CRPCa (mCRPCa). Front-line docetaxel has been administered to patients with CRPCa and mCRPCa. Nevertheless, docetaxel resistance after half a year of therapy has emerged as an urgent clinical concern in patients with CRPCa and mCRPCa. We verified the mechanism by which docetaxel-resistant PCa cells (DU/DX50) exhibited significant cell migration and expression of malignant tumor-related proteins. Our study shows that the biological activity of fucoidan has an important application for docetaxel-resistant PCa cells, inhibiting IL-1R by binding to P-selectin and reducing the expression levels of NF-κB p50 and Cox2 in this metastasis-inhibiting signaling pathway. Furthermore, the combined treatment of fucoidan and docetaxel showed significant anticancer and synergistic effects on the viability of DU/DX50 cells, which is relevant for overcoming the current limitations and improving treatment outcomes. Overall, fucoidan-based combination chemotherapy may exert beneficial effects and facilitate the treatment of docetaxel-resistant PCa.
ISSN:1660-3397
1660-3397
DOI:10.3390/md20090542