Background: Extracts from the marine algae Cymopolia barbata have previously shown promising pharmacological activity including antifungal, antitumor, antimicrobial, and antimutagenic properties. Even though extracts have demonstrated such bioactivity, isolated ingredients responsible for such bioactivity remain unspecified. In this study, we describe chemical characterization and evaluations of biological activity of prenylated bromohydroquinones (PBQ) isolated from the marine algae C. barbata for their cytotoxic and chemopreventive potential. Methods: The impact of PBQs on the viability of cell lines (MCF-7, HT29, HepG, and CCD18 Co) was evaluated using the MTS assay. In addition, their inhibitory impact on the activities of heterologously expressed cytochrome P450 (CYP) enzymes (CYP1A1, CYP1A2, CYP1B1, CYP2C19, CYP2D6, and CYP3A4) was evaluated using a fluorescent assay. Results: 7-Hydroxycymopochromanone (PBQ1) and 7-hydroxycymopolone (PBQ2) were isolated using liquid and column chromatography, identified using ¹ H and ¹³ C NMR spectra and compared with the spectra of previously isolated PBQs. PBQ2 selectively impacted the viability of HT29, colon cancer cells with similar potency to the known chemotherapeutic drug, fluorouracil (IC_50, 19.82 ± 0.46 μM compared to 23.50 ± 1.12 μM, respectively) with impact toward normal colon cells also being comparable (55.65 ± 3.28 compared to 55.51 ± 3.71 μM, respectively), while PBQ1 had no impact on these cells. Both PBQs had potent inhibition against the activities of CYP1A1 and CYP1B1, the latter which is known to be a universal marker for cancer and a target for drug discovery. Inhibitors of CYP1 enzymes by virtue of the prevention of activation of carcinogens such as benzo-a-pyrene have drawn attention as potential chemopreventors. PBQ2 potently inhibited the activity of CYP1B1 (IC₅₀ 0.14 ± 0.04 μM), while both PBQ1 and PBQ2 potently inhibited the activity of CYP1A1 (IC₅₀s of 0.39 ± 0.05 μM and 0.93 ± 0.26 μM, respectively). Further characterizations showed partial noncompetitive enzyme kinetics for PBQ2 with CYP1B1 with a K _i of 4.7 × 10^–3 ± 5.1 × 10^–4 μM and uncompetitive kinetics with CYP1A1 (K _i = 0.84 ± 0.07 μM); while PBQ1 displayed partial non competitive enzyme kinetics with CYP1A1 (K _i of 3.07 ± 0.69 μM), noncompetitive kinetics with CYP1A2 (K _i = 9.16 ± 4.68 μM) and uncompetitive kinetics with CYP1B1 (K _i = 0.26 ± 0.03 μM) . Conclusions: We report for the first time, two isolated ingredients from C. barbata, PBQ1 and PBQ2, that show potential as valuable chemotherapeutic compounds. A hydroxyl moiety resident in PBQ2 appears to be critical for selectivity and potency against the cancer colon cells, HT29, in comparison to the three other malignant cell lines studied. PBQs also show potency against the activities of CYP1 enzyme which may be a lead in chemoprevention. This study, the first on isolates from these marine algae, exemplifies the value of searching within nature for unique structural motifs that can display multiple biological activities.

Background: Immortalization of primary prostate epithelial cells (PrEC) with just hTERT expression is particularly inefficient in the absence of DNA tumor viral proteins or p16^INK4A knockdown. Materials and methods: Here, we describe the establishment of immortalized normal prostate epithelial cell line models using CRISPR technology to inactivate the CDKN2A locus concomitantly with ectopic expression of an hTERT transgene. Results: Using this approach, we have obtained immortal cell clones that exhibit fundamental characteristics of normal cells, including diploid genomes, near normal karyotypes, normal p53 and pRB cell responses, the ability to form non-invasive spheroids, and a non-transformed phenotype. Based on marker expression, these clones are of basal cell origin. Conclusions: Use of this approach resulted in the immortalization of independent clones of PrEC that retained normal characteristics, were stable, and non-transformed. Thus, this approach could be used for the immortalization of normal primary prostate cells. This technique could also be useful for establishing cell lines from prostate tumor tissues of different tumor grades and/or from patients of diverse ethnicities to generate cell line models that facilitate the study of the molecular basis of disease disparity.

Breast cancer (BCa) has long been a health burden to women across the globe. However, the burden is not equally carried across races. Though the manifestation and behavior of BCa differs among racial groups, the racial representation of models used in preclinical trials and clinical trial participants lacks this heterogeneity. Women of African Ancestry (WAA) are disproportionately afflicted by having an increased risk of developing BCas that are more aggressive in nature, and consequently suffer from poorer outcomes relative to women of European ancestry (WEA). Notwithstanding this, one of the most commonly used tools in studying BCa, cell lines, exhibit a sizeable gap in cell line derivatives of WEA relative to WAA. In this review, we summarize the available BCa cell lines grouped by race by major suppliers, American Type Culture Collection (ATCC) and the European Collection of Authenticated Cell Cultures (ECACC). Next, examined the enrollment of WAA in clinical trials for BCa. Of the cell lines found provided by ATCC and ECACC, those derived from WEA constituted approximately 80% and 94%, respectively. The disparity is mirrored in clinical trial enrollment where, on average, WEA made up more than 70% of participants in trials found where ancestry information was provided. As both experimental models and clinical trial participants primarily consist of WEA, results may have poorer translatability toward other races. This highlights the need for greater racial diversity at the preclinical and clinical levels to more accurately represent the population and strengthen the translatability of results.