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• W2887157957 abstract "The standard-of-care treatment for metastatic prostate cancer (PCa) is androgen deprivation therapy (ADT). Nevertheless, most tumors eventually relapse and develop into lethal castration-resistant prostate cancer (CRPC). Docetaxel is a FDA-approved agent for the treatment of CRPC; however, the tumor often quickly develops resistance to this drug. Thus, there is an immediate need for novel therapies to treat docetaxel-resistant PCa. In this study, we modified the structure of CIL-102 and investigated the efficacy of the derivatives against CRPC and docetaxel-resistant PCa. These novel CIL-102 derivatives inhibit CRPC tumorigenicity, including proliferation, migration and colony formation, and importantly, selectively inhibit CRPC cell proliferation over non-cancerous prostate epithelia. Computational modeling indicated the derivatives bind to β-tubulin and immunocytochemistry revealed the depolymerization of microtubules upon treatment. Western blot analyses reveal that pro-apoptotic and anti-oxidant pathways are activated, and MitoSOX and DCF-DA analyses confirmed increased reactive oxygen species (ROS) production upon treatments. Furthermore, CIL-102 derivatives effectively reduce the proliferation of docetaxel-resistant CR PCa cell lines. Our data indicate the potential of these compounds as promising therapeutic agents for CRPC as well as docetaxel-resistant CRPC." @default.
• W2887157957 created "2018-08-22" @default.
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• W2887157957 date "2018-11-01" @default.
• W2887157957 modified "2023-10-14" @default.
• W2887157957 title "Novel CIL-102 derivatives as potential therapeutic agents for docetaxel-resistant prostate cancer" @default.
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• W2887157957 doi "https://doi.org/10.1016/j.canlet.2018.07.039" @default.
• W2887157957 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6278836" @default.
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