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.

Synthesis and Biological Activity of 3-(Heteroaryl)quinolin-2(1H)-ones Bis-Heterocycles as Potential Inhibitors of the Protein Folding Machinery Hsp90

In the context of our SAR study concerning 6BrCaQ analogues as C-terminal Hsp90 inhibitors, we designed and synthesized a novel series of 3-(heteroaryl)quinolin-2(1H), of types 3, 4, and 5, as a novel class of analogues. A Pd-catalyzed Liebeskind–Srogl cross-coupling was developed as a convenient approach for easy access to complex purine architectures. This series of analogues showed a promising biological effect against MDA-MB231 and PC-3 cancer cell lines. This study led to the identification of the best compounds, 3b (IC50 = 28 µM) and 4e, which induce a significant decrease of CDK-1 client protein and stabilize the levels of Hsp90 and Hsp70 without triggering the HSR response.

How Does the pH of Tree Bark Change with the Presence of the Epiphytic Bryophytes from the Family Orthotrichaceae in the Interaction with Trunk Inclination?

The pH of tree bark is affected by many factors, amongst them epiphytic bryophytes changing in their active state environment. Thus, we hypothesized that bryophytes can change bark acidity, dependently of the inclination of the branches, as inclination affect the water regime and particle deposition. We measured the pH under bryophyte cushions and compared it to nearby naked bark. Additionally, we compared results with experimental bark covering with neutral cover. We found that the pH of naked bark declines with decreasing inclination of trunks. Although bryophyte cover did not generally change the pH of the bark, there was a significant interaction with inclination: with higher inclination, bryophytes decrease the pH reaction of bark, while with lower inclination they increase it. One possible explanation may lie in changes to alkaline particle deposition, or conversely in the acidification of the bark by leaching. In addition, an experiment with a neutral cover showed that naked bark covering would substantially increase pH. As, on average, bryophytes do not change the pH of bark, there can be mutual interference between the alkalizing effect of the bark cover itself and the acidifying biological effect of bryophytes.

Microencapsulation of an Extract of Sechium edule (Jacq.) Sw., with Antineoplastic Activity

Microencapsulation is a technique used in pharmaceuticals as an administration vehicle. Encapsulating secondary metabolites for therapeutic purposes has been promoted recently. Microencapsulation based on chitosan was developed for the methanol extract of cv. Perla negra (S. edule (Jacq.) Sw.) (Cucurbitaceae) fruits to evaluate its viability as an administration vehicle and to assess the possible negative interaction between the extract and chitosan. Microencapsulation was performed by coacervation, implementing a method with constant sonication. The microparticles obtained were registered by means of Scanning Electron Microscopy. The presence of the bioactive in aqueous medium was recorded for release tests, measuring with spectrophotometry its concentration as a function of time. The assessment of the biological effect of the microencapsulated extract was done on the HeLa cell line and control cells (lymphocytes). Microspheres with an average size of 20 µm and a loading capacity of 98% were obtained. The highest concentration of released extract was 24 µg mL−1 at 23 h. The mainly chitosan-based microspheres did not affect the antiproliferative activity of the extract of cv. Perla negra and proved to be a potential vehicle for its therapeutic administration. The empty microspheres made with chitosan also showed to have an antiproliferative effect, and those loaded with extract showed cellular inhibition (statistical IC50) of 8 µg mL−1 without affecting the lymphocytes. Chitosan does not interfere with the biological activity of the metabolites incorporated into the microspheres since they retain their inhibitory activity on proliferation in tumor cells, thus constituting a potential vehicle for the therapeutic administration of fruit extract.