Repurposing Thymoquinone as Therapy for Metastatic Castration-Resistant Prostate Cancer
Technical Report,01 Sep 2018,31 Aug 2019
Morehouse School of Medicine Inc. Atlanta United States
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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.
- Medicine and Medical Research