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Kumi-Diaka, J.

Publications and source records attributed to Kumi-Diaka, J..

2 recordsLinked to original sources
bioRxiv2021

Nucleoside antibiochemotherapy repressed the growth, chemoresistance, survival, and metastatic potentials of castration-resistant prostate cancer cells

There is currently no definitive cure for metastatic castration-resistant prostate cancer (mCRPC), therefore justifying the incessant need for more investigative studies to either repurpose old drugs or identify novel and effective therapeutics. In this study, we investigated the possible anticancer effects of two nucleoside antibiotics: puromycin and blasticidin. We hypothesized that the two antibiotics alone or combined with other drugs will inhibit prostate cancer (PCa) cell proliferation and metastasis and induce cell death via apoptosis. mCRPC cell lines (PC3 and DU145) with different p53-gene statuses were cultured and seeded in 96 well-plates, and thereafter treated with varying concentrations of puromycin and blasticidin (1 ng/mL - 100 g/mL) for 24 - 48 hours. Resazurin reduction and/or MTT assays were done to evaluate the treatment-induced effects on mCRPC cell viability and proliferation. The colony-forming assay measured the cell survival rate following treatment nucleoside antibiotics while scratch migration assay and dual-fluorescent microscopy assessed the effects on metastatic potential and cell death, respectively. The two antibiotics were combined with either paclitaxel, docetaxel, or cabazitaxel to check for synergism. Our results indicate that both antibiotics exhibit dose- and time-dependent anticancer effects on growth, survival, and metastasis of mCRPCs. PC3 cells were significantly more susceptible to both antibiotics compared to DU145 cells. Both cell lines were more susceptible to puromycin compared to blasticidin. Synergism was observed when each antibiotic compound was combined with any of the three taxanes. In conclusion, we have demonstrated that both puromycin and blasticidin could be explored for the treatment of mCRPC. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=179 SRC="FIGDIR/small/457225v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1bc2ae5org.highwire.dtl.DTLVardef@a438deorg.highwire.dtl.DTLVardef@191ad84org.highwire.dtl.DTLVardef@116d7c4_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗
bioRxiv2021

Integrative genomic and epigenomic analyses identified IRAK1 as a novel target for chronic inflammation-driven prostate tumorigenesis

The impacts of many inflammatory genes in prostate tumorigenesis remain understudied despite the increasing evidence that associates chronic inflammation with prostate cancer (PCa) initiation, progression, and therapy resistance. The overarching goal of this study was to identify dysregulated inflammatory genes that correlate with PCa progression and decipher their molecular mechanisms as well as clinical significance in PCa using integrative genomics, transcriptomics, and epigenomics approach. Our Weighted Gene Co-expression Analysis (WGCNA) and multivariate analysis identified 10 inflammatory genes: IRAK1, PPIL5/LRR1, HMGB3, HMGB2, TRAIP, IL1F5/IL36RN, ILF2, TRIM59, NFKBIL2/TONSL, and TRAF7 that were significantly associated with PCa progression. We explored the potentials of IRAK1 and other inflammatory genes as diagnostic and/or prognostic biomarkers by performing both KM survival and AUROC curve analyses. Our results indicate the clinical significance of these inflammatory genes in predicting the development and progression of PCa. IRAK1 was found to be overexpressed and hypomethylated in most PCa samples. A significantly high percentage of castration-resistant PCa (CRPC) and neuroendocrine PCa (NEPC) samples display copy number variations, especially amplification of the IRAK1 gene compared to the indolent prostate adenocarcinoma (PRAD) samples. Furthermore, we identified missense and frameshift mutations of IRAK1 in a few PRAD samples with potential functional implications. In conclusion, the results from this study suggest that IRAK1 dysregulation may be an important contributor to chronic prostatitis (inflammation) and PCa progression.

cancer biology↗