Distribution and Effects of Estrogen Receptors in Prostate Cancer: Associated Molecular Mechanisms

Estrogens are hormones that have been extensively presented in many types of cancer such as breast, uterus, colorectal, prostate, and others, due to dynamically integrated signaling cascades that coordinate cellular growth, differentiation, and death which can be potentially new therapeutic targets. Despite the historical use of estrogens in the pathogenesis of prostate cancer (PCa), their biological effect is not well known, nor their role in carcinogenesis or the mechanisms used to carry their therapeutic effects of neoplastic in prostate transformation. The expression and regulation of the estrogen receptors (ERs) ERα, ERβ, and GPER stimulated by agonists and antagonists, and related to prostate cancer cells are herein reviewed. Subsequently, the structures of the ERs and their splice variants, the binding of ligands to ERs, and the effect on PCa are provided. Finally, we also assessed the contribution of molecular simulation which can help us to search and predict potential estrogenic activities.

In Situ Detection of Hydrogen Sulfide in 3D-Cultured, Live Prostate Cancer Cells Using a Paper-Integrated Analytical Device

In this study, a paper-integrated analytical device that combined a paper-based colorimetric assay with a paper-based cell culture platform was developed for the in situ detection of hydrogen sulfide (H2S) in three-dimensional (3D)-cultured, live prostate cancer cells. Two kinds of paper substrates were fabricated using a simple wax-printing methodology to form the cell culture and detection zones, respectively. LNCaP cells were seeded directly on the paper substrate and grown in the paper-integrated analytical device. The cell viability and H2S production of LNCaP cells were assessed using a simple water-soluble tetrazolium salt colorimetric assay and H2S-sensing paper, respectively. The H2S-sensing paper showed good sensitivity (sensitivity: 6.12 blue channel intensity/μM H2S, R2 = 0.994) and a limit of quantification of 1.08 μM. As a result, we successfully measured changes in endogenous H2S production in 3D-cultured, live LNCaP cells within the paper-integrated analytical device while varying the duration of incubation and substrate concentration (L-cysteine). This paper-integrated analytical device can provide a simple and effective method to investigate H2S signaling pathways and drug screening in a 3D culture model.

Propylene Glycol Caprylate-Based Nanoemulsion Formulation of Plumbagin: Development and Characterization of Anticancer Activity

Plumbagin, a bioactive naphthoquinone, has demonstrated potent antitumor potential. However, plumbagin is a sparingly water-soluble compound; therefore, clinical translation requires and will be facilitated by the development of a new pharmaceutical formulation. We have generated an oil-in-water nanoemulsion formulation of plumbagin using a low-energy spontaneous emulsification process with propylene glycol caprylate (Capryol 90) as an oil phase and Labrasol/Kolliphor RH40 as surfactant and cosurfactant excipients. Formulation studies using Capryol 90/Labrasol/Kolliphor RH40 components, based on pseudoternary diagram and analysis of particle size distribution and polydispersity determined by dynamic light scattering (DLS), identified an optimized composition of excipients for nanoparticle formulation. The nanoemulsion loaded with plumbagin as an active pharmaceutical ingredient had an average hydrodynamic diameter of 30.9 nm with narrow polydispersity. The nanoemulsion exhibited long-term stability, as well as good retention of particle size in simulated physiological environments. Furthermore, plumbagin-loaded nanoemulsion showed an augmented cytotoxicity against prostate cancer cells PTEN-P2 in comparison to free drug. In conclusion, we generated a formulation of plumbagin with high loading drug capacity, robust stability, and scalable production. Novel Capryol 90-based nanoemulsion formulation of plumbagin demonstrated antiproliferative activity against prostate cancer cells, warranting thus further pharmaceutical development.