In the era of targeted therapeutics, the inadequate representation of Black populations in prostate cancer models limits effective drug screening. In this study, we introduce ACRJ-PC28, a novel Afro-Caribbean prostate cancer cell line, and evaluate its responses to five anticancer drugs (docetaxel, cabazitaxel, abiraterone, olaparib, and enzalutamide) and betaine. We compare these responses with those of established prostate cancer cell lines from Black (MDA-PCA-2b) and White (DU-145 and PC-3) donors using three distinct viability assays. We observed ancestry-dependent drug sensitivities: abiraterone showed remarkable selectivity for ACRJ-PC28 (IC50 = 1.10 μmol/L), being 4.6- to 13.1-fold more potent than in other cell lines, whereas enzalutamide demonstrated pronounced racial differences, being 3 to 5 times less effective in cell lines from Black donors (IC50 = 206 μmol/L for ACRJ-PC28; 104 μmol/L for MDA-PCA-2b) versus cell lines from White donors (IC50 = 37 μmol/L for PC-3; 48 μmol/L for DU-145). RNA sequencing analysis revealed consistent underexpression of TNF family genes, particularly TNFRSF14, in prostate cancer cells from Black donors correlating with differential drug responses. Despite underexpressing AR, the ACRJ-PC28 line exhibited exceptional sensitivity to abiraterone, consistent with clinical observations that Black patients with prostate cancer respond better to this therapy. This aligns with its neuroendocrine phenotype in the source patient, who succumbed within 1 year despite androgen deprivation therapy. Our findings suggest that incorporating diverse prostate cancer models in preclinical screening could guide personalized treatment strategies for Black patients who experience disproportionate prostate cancer mortality by identifying ancestry-specific drug vulnerabilities that inform optimal therapeutic combinations. Significance: This study introduces ACRJ-PC28, the first Afro-Caribbean prostate cancer cell line, revealing ancestry-dependent drug sensitivities that could explain differential clinical outcomes. The findings demonstrate critical gaps in current preclinical models and support incorporating diverse cell lines to develop personalized treatment strategies for underrepresented populations experiencing disproportionate cancer mortality.

A benzothiazolium-derived optical sensor, (E)-3-ethyl-2-(2,4,6-trimethoxystyryl) benzo[d]thiazol-3-ium iodide (ETBI), was synthesized for the selective detection of cyanide ions (CN⁻). Its structure was confirmed through ¹H NMR, ¹³C NMR, HRMS, IR, and single-crystal XRD analysis. ETBI exhibits a dual-mode optical response, displaying significant absorption, fluorescence quenching, and a distinct naked-eye-detectable color change from pale yellow to colorless. This change results from nucleophilic addition of CN⁻ to the benzothiazolium ring, which disrupts the π-conjugated system and inhibits intramolecular charge transfer (ICT). The job plot indicated a 1 : 1 binding stoichiometry between ETBI and CN⁻, with an association constant (K_a) of 2.86 × 10⁴ M⁻¹. The probe ETBI demonstrated high sensitivity, achieving a detection limit of 0.49 μM, well below the World Health Organization (WHO) guideline for CN⁻ in drinking water. Furthermore, ETBI was successfully applied in fluorescence imaging of intracellular CN⁻ in HeLa cells and using Whatman filter paper as a test strip.

Metastatic prostate cancer (mPCa) is a leading cause of mortality, partly due to its resistance to anti-androgens like enzalutamide. Snail can promote this resistance by increasing full-length AR and AR-V7. High Mobility Group AT-hook 2 (HMGA2), a DNA-binding protein upstream of Snail, is crucial in proliferation and epithelial–mesenchymal transition (EMT). This study examines HMGA2’s role in enzalutamide resistance. LNCaP and 22Rv1 cells overexpressing wild-type HMGA2, but not truncated HMGA2, showed EMT. Both variants led to a decreased sensitivity to enzalutamide but not alisertib compared to Neo control cells. The overexpression of HMGA2 did not alter AR expression. Enzalutamide-resistant C4-2B cells (C4-2B MDVR) had higher HMGA2 and AR/AR variant expression than enzalutamide-sensitive C4-2B cells but remained sensitive to alisertib. The HMGA2 knockdown in C4-2B MDVR cells increased sensitivity to both enzalutamide and alisertib without changing AR expression. A clinical analysis via cBioPortal revealed HMGA2 alterations in 3% and AR alterations in 59% of patients. The HMGA2 changes were linked to treatments like enzalutamide, abiraterone, or alisertib, with amplifications more prevalent in bone, lymph node, and liver metastases. Conclusively, HMGA2 is a potential biomarker for enzalutamide resistance in mPCa, independent of Snail and AR signaling, and alisertib may be an effective treatment for mPCa that expresses HMGA2.

In the era of targeted therapeutics, the inadequate representation of Black populations in prostate cancer models limits effective drug screening. In this study, we introduce ACRJ-PC28, a novel Afro-Caribbean prostate cancer cell line, and evaluate its responses to five anticancer drugs (docetaxel, cabazitaxel, abiraterone, olaparib, and enzalutamide) and betaine. We compare these responses with those of established prostate cancer cell lines from Black (MDA-PCA-2b) and White (DU-145 and PC-3) donors using three distinct viability assays. We observed ancestry-dependent drug sensitivities: abiraterone showed remarkable selectivity for ACRJ-PC28 (IC50 = 1.10 μmol/L), being 4.6- to 13.1-fold more potent than in other cell lines, whereas enzalutamide demonstrated pronounced racial differences, being 3 to 5 times less effective in cell lines from Black donors (IC50 = 206 μmol/L for ACRJ-PC28; 104 μmol/L for MDA-PCA-2b) versus cell lines from White donors (IC50 = 37 μmol/L for PC-3; 48 μmol/L for DU-145). RNA sequencing analysis revealed consistent underexpression of TNF family genes, particularly TNFRSF14, in prostate cancer cells from Black donors correlating with differential drug responses. Despite underexpressing AR, the ACRJ-PC28 line exhibited exceptional sensitivity to abiraterone, consistent with clinical observations that Black patients with prostate cancer respond better to this therapy. This aligns with its neuroendocrine phenotype in the source patient, who succumbed within 1 year despite androgen deprivation therapy. Our findings suggest that incorporating diverse prostate cancer models in preclinical screening could guide personalized treatment strategies for Black patients who experience disproportionate prostate cancer mortality by identifying ancestry-specific drug vulnerabilities that inform optimal therapeutic combinations.Significance:This study introduces ACRJ-PC28, the first Afro-Caribbean prostate cancer cell line, revealing ancestry-dependent drug sensitivities that could explain differential clinical outcomes. The findings demonstrate critical gaps in current preclinical models and support incorporating diverse cell lines to develop personalized treatment strategies for underrepresented populations experiencing disproportionate cancer mortality.

DEGs: Black-derived vs White-derived PCa Lines. This table documents the 633 genes differentially expressed between Black-derived (ACRJ-PC28 and MDA-PCA-2b) and White-derived (DU-145 and PC-3) PCa cell lines. The data includes gene identifiers, annotations, expression fold changes, statistical significance values, and functional pathway associations. The table highlights genes consistently underexpressed in Black-derived cell lines, including TNFRSF14 and other genes involved in androgen signaling, DNA damage repair, and growth factor pathways that may contribute to the observed ancestry-dependent differences in drug sensitivity, particularly to androgen-targeted therapies and PARP inhibitors.