Repurposing Thymoquinone as Therapy for Metastatic Castration-Resistant Prostate Cancer

Abstract

The major goal of this project is to elucidate the mechanism of action of thymoquinone (TQ) against docetaxel (DTX)-resistant metastatic castration-resistant prostate cancer (mCRPC). We formulated a novel TQ nanoparticles (NPs) that are capable of rapid clinical translation; we utilized a highly innovative-patented NP platform, the planetary ball-milling (PBM) platform. In this study, we identified the highly expressed ATP-binding cassette (ABC) transporters, that play a major role in drug efflux activity, in docetaxel resistance cells (C4-2B-R and LNCaP-R). We found that these efflux proteins were downregulated when targeted with PSMA aptamer (A10) conjugated PBM -TQ -NPs and re-sensitizes docetaxel resistant cells towards cell death. In addition, we have also identified PSMA-mediated cellular uptake of PBM NPs in prostate cancer cells and an abundant number of internalized PBM nanoparticle were found through PSMA receptor in PSMA+ cells. Altogether, our engineered PBM NPs displayed, specificity and sensitivity to PSMA receptor, and suggest a novel strategy for treating prostate cancer.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2019
Accession Number
AD1094227

Entities

People

  • Rajesh Singh

Organizations

  • Morehouse School of Medicine

Tags

DTIC Thesaurus Topics

  • Antineoplastic Agents
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Chemotherapy
  • Chlorides
  • Cytoskeleton
  • Diseases And Disorders
  • Engineering
  • Enzyme Inhibitors
  • Gene Expression
  • Materials
  • Medical Personnel
  • Nanoparticles
  • Neoplasms
  • Polymerase Chain Reaction
  • Prostate Cancer

Fields of Study

  • Biology

Readers

  • Oncology (Cancer Research).
  • Prostate Cancer Biology.

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech