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Breast cancer (BC) and prostate cancer (PC) are at the top of the list when it comes to the most common types of cancers worldwide. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is important, in that it strongly influences the development and progression of these tumors. Previous studies have emphasized the key role of inhibitors of the PIK3/AKT/mTOR signaling pathway in the treatment of BC and PC, and it remains to be a crucial method of treatment. In this review, the inhibitors of these signaling pathways are compared, as well as their effectiveness in therapy and potential as therapeutic agents. The use of these inhibitors as polytherapy is evaluated, especially with the use of hormonal therapy, which has shown promising results., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Masson SAS.)

The role of cyclins in hormone-dependent neoplasms is crucial in the development of the disease that is resistant to first-line therapy, as the example of breast cancer shows. However, in prostate cancer, cyclins are studied to a lesser extent. There are some well-described molecular pathways, including cyclins A1 and D1 signaling, however the role of other cyclins, e.g., D2, D3, E, and H, still requires further investigation. Recent studies indicate that cyclins regulate various cellular processes, not only the cell cycle. Furthermore, they remain in cross-talk with many other signaling pathways, e.g., MAPK/ERK, PI3K/Akt, and Notch. The androgen signaling axis, which is pivotal in prostate cancer progression, interferes with cyclin pathways at many levels. This article summarizes current knowledge on the influence of cyclins on prostate cancer progression by describing interactions between the androgen receptor and cyclins, as well as mechanisms underlying the development of resistance to currently used therapies., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Prostate cancer (PC) is the second most common tumor in males. The search for appropriate therapeutic options against advanced PC has been in process for several decades. Especially after cessation of the effectiveness of hormonal therapy (i.e., emergence of castration-resistant PC), PC management options have become scarce and the prognosis is poor. To overcome this stage of disease, an array of natural and synthetic substances underwent investigation. An interesting and promising class of compounds constitutes the derivatives of natural retinoids. Synthesized on the basis of the structure of retinoic acid, they present unique and remarkable properties that warrant their investigation as antitumor drugs. However, there is no up-to-date compilation that consecutively summarizes the current state of knowledge about synthetic retinoids with regard to PC. Therefore, in this review, we present the results of the experimental studies on synthetic retinoids conducted within the last decade. Our primary aim is to highlight the molecular targets of these compounds and to identify their potential promise in the treatment of PC.

Purpose: Epithelial-mesenchymal (EMT) transition plays an important role in metastasis and is accompanied by an upregulation of N-cadherin expression. A new nanoparticulate system (SPION/CCh/N-cad) based on superparamagnetic iron oxide nanoparticles, stabilized with a cationic derivative of chitosan and surface-modified with anti-N-cadherin antibody, was synthetized for the effective capture of N-cadherin expressing circulating tumor cells (CTC)., Methods: The morphology, physicochemical, and magnetic properties of the system were evaluated using dynamic light scattering (DLS), fluorescence spectroscopy, Mössbauer spectroscopy, magnetometry, and fluorescence spectroscopy. Atomic force microscopy (AFM), confocal microscopy and flow cytometry were used to study the interaction of our nanoparticulate system with N-cadherin expressed in prostate cancer cell lines (PC-3 and DU 145). A purpose-built cuvette was used in the cancer cell capture experiments., Results: The obtained nanoparticles were a spherical, stable colloid, and exhibited excellent magnetic properties. Biological experiments confirmed that the novel SPION/CCh/N-cad system interacts specifically with N-cadherin present on the cell surface. Preliminary studies on the magnetic capture of PC-3 cells using the obtained nanoparticles were successful. Incubation times as short as 1 minute were sufficient for the synthesized system to effectively bind to the PC-3 cells., Conclusion: Results obtained for our system suggest a possibility of using it to capture CTC in the flow conditions., Competing Interests: Dr Anna Karewicz reports grants from Narodowe Centrum Nauki, during the conduct of the study. The authors report no other conflicts of interest in this work., (© 2021 Karnas et al.)

Background/aim: During cancer progression cells undergo epithelial-to-mesenchymal transition (EMT). Although EMT is a complex process, recently, it has been reported that CD146 overexpression in prostate cancer cells is sufficient to induce mesenchymal phenotype. The following study aimed to investigate whether the expression of CD146 is altered by an epigenetic modifier in prostate cancer cells, in vitro., Materials and Methods: Three human prostate cancer cell lines were treated with 5-aza-2-deoxycytidine; the expression of CD146 and EMT-related factors was analyzed by RT-PCR and western Blot. The methylation status of the CD146 promoter area was assessed using bisulfite sequencing., Results: Our data showed that, the expression of CD146 was evidently increased in all three studied cell lines in response to a demethylating agent, both at the mRNA and protein level, suggesting epigenetic regulation of the analyzed gene. However, there was no methylation in the studied CpG island in CD146 gene promoter. Moreover, the demethylating agent induced the expression of EMT-related transcription factors (SNAI1, SNAI2, TWIST1 and ZEB1), the pattern of which differed among the cell lines, as well as alterations in cell morphology; altogether accounting for the mesenchymal phenotype., Conclusion: The demethylating agent 5-aza-2-deoxycytidine triggers the expression of CD146 in prostate cancer cells independently on the methylation status of the analyzed CpG island fragment in CD146 gene promoter. Moreover, demethylation treatment induces a mesenchymal profile in prostate cancer cells., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

NutramilTM Complex is a multicomponent food product that meets the requirements of a food for special medical purpose. As a complete, high-energy diet it consists of properly balanced nutrients, vitamins and minerals. The aim of this study was to assess the effect of NutramilTM Complex on breast and prostate carcinoma cells. Our results showed that NutramilTM Complex reduced the viability and proliferation of breast and prostate cancer cells and that this process was associated with the induction of apoptosis via activation of caspase signalling. Data showed elevated levels of p53 tumour suppressor, up-regulation of p38 MAPK and SAPK / JNK proteins and downregulation of anti-apoptotic ERK1/2, AKT1 and HSP27. Treatment with NutramilTM Complex also affected the expression of the BCL2 family genes. Results also showed down-regulation of anti-apoptotic BCL-2 and up-regulation of pro-apoptotic members such as BAX, BAD, BID. In addition, we also observed regulation of many other genes, including Iκβα, Chk1 and Chk2, associated with apoptotic events. Taken together, our results suggest activation of the mitochondrial apoptotic pathway as most likely mechanism of anti-carcinogenic activity of NutramilTM Complex.

This study aimed to investigate rapid effect of anti-androgen 2-hydroxyflutamide (HF) on cadherin/catenin complex and androgen receptor (AR) phosphorylation in prostate cancer cell lines. In addition, a role of PI3K/Akt and MAPK/ERK1/2 pathways in mediating these effects was explored. We have demonstrated that in androgen-sensitive LNCaP cells HF induced rapid increase of E-cadherin phosphorylation at Ser 838/840 (p<0.05) in MAPK/ERK1/2-dependent manner, whereas phosphorylation of β-catenin at Tyr 654 was unchanged. Concomitantly, the reduction of the level of AR phosphorylated at Ser210/213 was found (p<0.01). In androgen-independent PC3 cells HF decreased Tyr 860 N-cadherin and Tyr 645 β-catenin phosphorylation (p<0.01), acting via both MAPK/ERK1/2 and PI3K/Akt pathways. Further, we evidenced that MAPK/ERK1/2 and PI3K/Akt pathways were differentially influenced by HF in LNCaP and PC3 cells. In LNCaP cells, both Akt (p<0.01) and ERK1/2 (p<0.001) phosphorylation were negatively regulated and this effect was mediated by Raf-1 (p<0.05). In contrast, in PC3 cells HF stimulated Akt (p<0.001) and ERK1/2 (p<0.001) activation, but had no effect on the crosstalk between PI3K/Akt and MEK/ERK1/2 pathways at the Raf-1 kinase level. Our findings expand the role of anti-androgen into non-genomic signaling, creating a link between anti-androgen action and phosphorylation of adherens junction proteins in prostate cancer cells., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The aim of this research was to find out whether the passage number effect may influence on the PC-3 cells (the human prostate cancer line derived from bone metastases) response to proton radiation. 2 MeV horizontally focused proton microbeam was used as a radiation source. The cells were treated with a counted number of H(+) ions (50-8000) corresponding to doses of 1.3-209 Gy/cell. For comparison, cell death was also induced by UVC radiation. All cells were stained with Hoechst 33342 and propidium iodide and visualized under a fluorescence microscope. Necrosis was observed at: a) 8000 protons per cell (corresponding to ∼209 Gy/cell) after 2-4 passages, b) 3200 protons per cell (corresponding to ∼84 Gy/cell) for cells after 11-14 passages and c) only 800 protons per cell (corresponding to ∼2 Gy/cell ) after 47-50 passages. Apoptosis was efficiently induced, by protons, only in cells after 50 passages. The results showed that the laboratory conditions affected cellular response of PC-3 cell line to the proton irradiation. The cellular response to the radiation treatment strongly depends on number of passages.