menaquinone-6 and Prostatic-Neoplasms--Castration-Resistant

Abiraterone acetate (AA) is an inhibitor of androgen biosynthesis, though this cannot fully explain its efficacy against androgen-independent prostate cancer. Here, we demonstrate that androgen deprivation therapy depletes androgen-utilizing Corynebacterium spp. in prostate cancer patients and that oral AA further enriches for the health-associated commensal, Akkermansia muciniphila. Functional inferencing elucidates a coinciding increase in bacterial biosynthesis of vitamin K2 (an inhibitor of androgen dependent and independent tumor growth). These results are highly reproducible in a host-free gut model, excluding the possibility of immune involvement. Further investigation reveals that AA is metabolized by bacteria in vitro and that breakdown components selectively impact growth. We conclude that A. muciniphila is a key regulator of AA-mediated restructuring of microbial communities, and that this species may affect treatment response in castrate-resistant cohorts. Ongoing initiatives aimed at modulating the colonic microbiota of cancer patients may consider targeted delivery of poorly absorbed selective bacterial growth agents.

Topics: Abiraterone Acetate; Akkermansia; Androgen Antagonists; Androgens; Bacteria; Feces; Gastrointestinal Microbiome; Humans; Male; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; RNA, Ribosomal, 16S; Verrucomicrobia; Vitamin K 2

The aim of this study was to evaluate the therapeutic effects of vitamin K2 (VK2) on castration-resistant prostate cancer (CRPC) and its anti-cancer mechanisms in a pre-clinical study using a VCaP cell line (ATCC

Topics: Antineoplastic Agents; Apoptosis; Blotting, Western; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cellular Senescence; Dairy Products; Humans; Male; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Reactive Oxygen Species; Signal Transduction; Vitamin K 2

Hepatoma-derived growth factor (HDGF) is a heparin-binding growth factor, which has previously been shown to be expressed in a variety of cancers. HDGF overexpression has also previously been correlated with a poor prognosis in several cancers. The significance of HDGF in prostate cancer, however, has not been investigated. Here, we show that HDGF is overexpressed in both androgen-sensitive LNCaP cells and androgen-insensitive DU145, 22RV1, and PC-3 cells. Forced overexpression enhanced cell viability of RWPE-1 cells, whereas HDGF knockdown reduced cell proliferation in human prostate cancer cells. We also show that HDGF may serve as a survival-related protein as ectopic overexpression of HDGF in RWPE cells up-regulated the expression of antiapoptosis proteins cyclin E and BCL-2, whereas simultaneously down-regulating proapoptotic protein BAX. Western blot analysis also showed that HDGF overexpression modulated the activity of phospho-AKT as well as NF-kB, and these results correlated with in vitro migration and invasion assays. We next assessed the therapeutic potential of HDGF inhibition with a HDGF monoclonal antibody and vitamin k

Topics: Adenocarcinoma; Androgens; Antibodies, Monoclonal; Apoptosis; Cell Division; Cell Line, Tumor; Cell Survival; Cell Transformation, Neoplastic; Drug Screening Assays, Antitumor; Epithelial Cells; Gene Expression Regulation, Neoplastic; Humans; Intercellular Signaling Peptides and Proteins; Male; Molecular Targeted Therapy; Neoplasm Proteins; Neoplasms, Hormone-Dependent; NF-kappa B; Prostate; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Recombinant Proteins; RNA Interference; RNA, Small Interfering; Vitamin K 2