Sweet cherries (Prunus avium L.) are among the most appreciated fruits worldwide because of their organoleptic properties and nutritional value. The accurate phytochemical composition and nutritional value of sweet cherries depends on the climatic region, cultivar, and bioaccessibility and bioavailability of specific compounds. Nevertheless, sweet cherry extracts are highly enriched in several phenolic compounds with relevant bioactivity. Over the years, technological advances in chemical analysis and fields as varied as proteomics, genomics and bioinformatics, have allowed the detailed characterization of the sweet cherry bioactive phytonutrients and their biological function. In this context, the effect of sweet cherries on suppressing important events in the carcinogenic process, such as oxidative stress and inflammation, was widely documented. Interestingly, results from our research group and others have widened the action of sweet cherries to many hallmarks of cancer, namely metabolic reprogramming. The present review discusses the anticarcinogenic potential of sweet cherries by addressing their phytochemical composition, the bioaccessibility and bioavailability of specific bioactive compounds, and the existing knowledge concerning the effects against oxidative stress, chronic inflammation, deregulated cell proliferation and apoptosis, invasion and metastization, and metabolic alterations. Globally, this review highlights the prospective use of sweet cherries as a dietary supplement or in cancer treatment.

Despite their different geographical distribution Achillea millefolium L. and Achillea erba-rotta subsp. moschata (Wulfen) I. Richardson are characterized by a consolidated traditional knowledge. Although this is not their first traditional use, they have also long been used as ingredients for skin healing and skin care. The aim of this work was to characterize the two Achillea species from a chemical and biomolecular point of view in order to find a simple tool for their discrimination. At the same time, the biological activity of the extracts as inhibitors of the enzymes tyrosinase and elastase and as antimicrobial agents was evaluated. The biomolecular analysis was performed on the DNA region trnL-F. The hydroalcholic (EtOH50 %) extracts were quali-quantitatively characterized by HPLC-PDA-MS/MS and tested for their inhibitory effect on the enzymes tyrosinase and elastase as well as for their antimicrobial activity. Cytotoxicity towards human fibroblasts was tested to evaluate their safety for potential applications. Restriction Fragment Length Polymorphism (RFLP) analysis of the trnL-F DNA region was a useful tool for species discrimination. Both extracts are rich in polyphenols and showed moderate tyrosinase (26-5 %) and elastase (22-14 %) inhibitory activity at 17 μg/mL. They were also able to inhibit the growth of the bacteria and yeasts studied, generally exhibiting cytotoxicity to human fibroblasts at concentrations of 500 μg/mL or higher. The hydroalcoholic extracts from the aerial parts of A. millefolium and A. erba-rotta subsp. moschata can be considered good candidates for the cosmetic and health sectors, also supporting the traditional use of these species in the treatment of skin diseases.

Obesity-dysregulated periprostatic adipose tissue (PPAT) has been implicated in the aggressiveness of prostate cancer (PCa). On the other hand, obesity has been linked to environmental influences, namely, the endocrine-disrupting chemicals capable of promoting adipogenesis and fat accumulation (obesogens). However, it is unknown whether obesogens can induce PPAT dysfunction, disrupting its crosstalk with PCa cells. The present study hypothesises that obesogens can target the PPAT, affecting its secretory activity and contributing to the development or aggressiveness of PCa. Through in vivo, ex vivo approaches and conditioned medium (CM) assays, we demonstrated that exposure to tributyltin (TBT), the first described obesogen, induced a PPAT "obese" phenotype, with adipocyte enlargement and enhanced secretion of leptin and C-C motif chemokine ligand 7 (CCL7). TBT-PPAT altered prostate cell fate, enhancing their viability, proliferation and migration, and reducing apoptotic rate. Moreover, it was shown that the TBT-PPAT secretome promoted the migration of prostate cells involving the C-C motif chemokine receptor 3 (CCR3). Overall, this study demonstrated the biological significance of TBT exposure, bringing functional evidence on the contribution of PPAT obesogenic dysregulation to prostate carcinogenesis. Moreover, it highlights the differences that may exist in PCa monitoring and treatment in obese vs. lean patients, pointing out the modulation of PPAT activity as a therapeutic target.

Background/Objectives: Regucalcin (RGN) is a calcium-binding protein and an oestrogen target gene, which has been shown to play essential roles beyond calcium homeostasis. Decreased RGN expression was identified in several cancers, including prostate cancer (PCa). However, it is unknown if the loss of RGN is a cause or a consequence of malignancy. Also, it needs confirmation if RGN oestrogenic regulation occurs through the G-protein-coupled oestrogen receptor (GPER). This study investigates how RGN knockdown affects prostate cell fate and metabolism and highlights the GPER/RGN interplay in PCa. Methods: Bioinformatic analysis assessed the relationship between RGN expression levels and patients’ outcomes. RGN knockdown (siRNA) was performed in non-neoplastic prostate and castration-resistant PCa. Wild-type and RGN knockdown PCa cells were treated with the GPER agonist G1. Viability (MTT), proliferation (Ki-67 immunocytochemistry), apoptosis (caspase-3-like activity) and migration (Transwell assays) were evaluated. Spectrophotometric analysis was used to determine glucose consumption, lactate production and lactate dehydrogenase activity. Lipid content was assessed using the Oil Red assay. Results/conclusions: Bioinformatic analysis showed that the loss of RGN correlates with the development of metastatic PCa and poor survival outcomes. RGN knockdown induced a cancer-like phenotype in PNT1A cells, indicated by increased cell viability and proliferation and reduced apoptosis. In DU145 PCa cells, RGN knockdown augmented migration and enhanced the glycolytic profile, which indicates increased aggressiveness, in line with patients’ data. GPER activation modulated RGN expression in PCa cells and RGN knockdown in DU145 cells influenced GPER actions, which highlighted an interplay between these molecular players with relevance for their potential use as biomarkers or therapeutic targets.

Background: Periprostatic adipose tissue (PPAT) has been shown to play a significant role in prostate cancer (PCa) development and progression. This relationship is further exacerbated by obesity, as PPAT-secreted factors increase PCa aggressiveness and have also been implicated in chemotherapy resistance. Therefore, identifying the molecular mediators of PPAT–prostate interorgan communication and the factors that disrupt this crosstalk is pivotal for better disease management. Obesogens, i.e., endocrine-disrupting chemicals that dysregulate adipose tissue towards an “obese” phenotype, have recently been implicated in disrupting this crosstalk, with an impact on prostate cell fate. Objectives: This study aimed to investigate whether obesogenic dysregulation of human PPAT secretory activity affects PCa cell viability and their response to docetaxel and cabazitaxel. Methods/Results: Through ex vivo culture of human PPAT and conditioned medium assays, we demonstrated that exposure to the model obesogen tributyltin (TBT) induced an “obese” phenotype in human PPAT, characterised by adipocyte enlargement and increased secretion of leptin and C-C motif chemokine ligand 7. The TBT-treated PPAT secretome enhanced cell viability and decreased the sensitivity of PCa cells to taxanes. Conclusions: This study provides preliminary evidence that lays the groundwork for future investigations, dissecting the molecular pathways underpinning prostate carcinogenesis and resistance to chemotherapy induced by obesogen-dysregulated PPAT.

Purpose of Review: This review addresses the contribution of obesogenic endocrine-disrupting chemicals (EDCs) to prostate carcinogenesis. It provides an in-depth overview of obesogens, tracing their mechanisms of action and effects impacting prostate cell fate. The direct effects of obesogens in disrupting adipose tissue and metabolic homeostasis, as well as disturbing prostate cells, are discussed, along with the potential indirect effects mediated by the dysregulation of the adipose tissue. Recent Findings: Obesogens represent a group of EDCs that interfere with endocrine and metabolic processes, underpinning the spread of obesity. Moreover, the ubiquitous presence in the environment, the ability to accumulate in adipose tissue and the broad range of effects targeting several biological pathways highlight that obesogens can be detrimental to human health beyond their action on promoting obesity. Prostate cancer (PCa) is a hormone-dependent cancer for which environmental influences and obesity are established risk factors, with emerging evidence suggesting that obesogens may affect its development and progression. Summary: The available data indicate that obesogens may contribute to the development of PCa. They can have direct actions in prostate cells modulating signalling pathways that drive tumour aggressiveness. Moreover, the adipose tissue dysregulated by obesogens can acquire an obesity-like phenotype, which may play a crucial role in facilitating tumour growth. Further research is needed to clarify the liaison between obesogen-induced dysregulation of the periprostatic adipose tissue depot and PCa aggressiveness. Unravelling this complex crosstalk will be pivotal for identifying novel therapeutic strategies and preventing aggressive PCa, especially in obese patients.