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We focused on the biomechanical and morphological characteristics of prostate cancer cells and their changes resulting from the effect of docetaxel, cisplatin, and long-term zinc supplementation. Cell population surviving the treatment was characterized as follows: cell stiffness was assessed by atomic force microscopy, cell motility and invasion capacity were determined by colony forming assay, wound healing assay, coherence-controlled holographic microscopy, and real-time cell analysis. Cells of metastatic origin exhibited lower height than cells derived from the primary tumour. Cell dry mass and CAV1 gene expression followed similar trends as cell stiffness. Docetaxel- and cisplatin-surviving cells had higher stiffness, and decreased motility and invasive potential as compared to non-treated cells. This effect was not observed in zinc(II)-treated cells. We presume that cell stiffness changes may represent an important overlooked effect of cisplatin-based anti-cancer drugs. Atomic force microscopy and confocal microscopy data images used in our study are available for download in the Zenodo repository (https://zenodo.org/, Digital Object Identifiers:10.5281/zenodo.1494935).

Differences in the antioxidant system, apoptotic mechanism and in cell cycle between prostatic cell lines could partially elucidate the development of cisplatin resistance. The aim of this study was to identify the most characteristic parameter for a particular cell line and/or a particular cisplatin treatment using a general regression model and to assess whether it is possible to use measured parameters as markers of cisplatin resistance. This study integrates the results of viability, antioxidant, flow cytometric and quantitative PCR assays in order to characterize the resistance of prostate cancer to cisplatin. Cell growth using metabolic- (MTT) and impedance-based assays, the expression of key cell death signaling proteins (p53, Bax and Bcl-2), cell cycle, activity of antioxidant system-related proteins (superoxide dismutase, glutathione peroxidase, glutathione reductase and metallothionein) and free radical scavenging capacity assays [free radicals (FR), ferric reducing antioxidant power (FRAP), ABTS] were analyzed in the cell lines 22Rv1, PC-3 and PNT1A with respect to rising concentrations (0-150 µM) and different length of cisplatin treatment (12-72 h). The non-functional-p53 PC-3 cell line showed decreased BAX (p<0.05) and, in contrast to PNT1A and 22Rv1, no cisplatin-induced effects on cell cycle. All cell lines showed increasing levels of free radical scavenging activity by ABTS, FRAP and FR assays in a time- and dose-dependent manner (r>0.76 at p<0.001 for ABTS, FRAP and FR at p<0.001). PC-3 showed increased (p<0.05) levels of free radical scavenging activity by ABTS and FR methods. These findings, together with significantly elevated MT, decreased p53 and Bax indicate PC-3 to be cisplatin-resistant. The differences in the antioxidant system and apoptotic mechanisms in PC-3 cells may elucidate the development of cisplatin resistance and indicate that this cell line may be further studied as a model of cytostatic resistance.

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Metals are known for playing essential roles in human physiology. Copper and zinc are trace elements closely dependent on one another and are involved in cell proliferation, growth, gene expression, apoptosis and other processes. Their homeostasis is crucial and tightly controlled by a resourceful system of transporters and transport proteins which deliver copper and zinc ions to their target sites. Abnormal zinc and copper homeostasis can be seen in a number of malignancies and also in head and neck cancer. Imbalance in this homeostasis is observed as an elevation or decrease of copper and zinc ions in serum or tissue levels in patients with cancer. In head and neck cancer these altered levels stand out from those of other malignancies which makes them an object of interest and therefore zinc and copper ions might be a good target for further research of head and neck cancer development and progression. This review aims to summarize the physiological roles of copper and zinc, its binding and transport mechanisms, and based on those, its role in head and neck cancer. To provide stronger evidence, dysregulation of levels is analysed by a meta-analytical approach.

The effects of sarcosine on the processes driving prostate cancer (PCa) development remain still unclear. Herein, we show that a supplementation of metastatic PCa cells (androgen independent PC-3 and androgen dependent LNCaP) with sarcosine stimulates cells proliferation in vitro. Similar stimulatory effects were observed also in PCa murine xenografts, in which sarcosine treatment induced a tumor growth and significantly reduced weight of treated mice (p < 0.05). Determination of sarcosine metabolism-related amino acids and enzymes within tumor mass revealed significantly increased glycine, serine and sarcosine concentrations after treatment accompanied with the increased amount of sarcosine dehydrogenase. In both tumor types, dimethylglycine and glycine-N-methyltransferase were affected slightly, only. To identify the effects of sarcosine treatment on the expression of genes involved in any aspect of cancer development, we further investigated expression profiles of excised tumors using cDNA electrochemical microarray followed by validation using the semi-quantitative PCR. We found 25 differentially expressed genes in PC-3, 32 in LNCaP tumors and 18 overlapping genes. Bioinformatical processing revealed strong sarcosine-related induction of genes involved particularly in a cell cycle progression. Our exploratory study demonstrates that sarcosine stimulates PCa metastatic cells irrespectively of androgen dependence. Overall, the obtained data provides valuable information towards understanding the role of sarcosine in PCa progression and adds another piece of puzzle into a picture of sarcosine oncometabolic potential.

Prostate cancer cells control energy metabolism by chelating intracellular zinc. Thus, zinc delivery has been a popular therapeutic approach for prostate cancer. Here, we propose the use of the membrane-penetrating peptide Novicidin connected to zinc-Schiff base as a carrier vehicle for the delivery of zinc to prostate cells. Mass spectrometry, electrochemistry and spectrophotometry confirmed the formation/stability of this complex and provided insight regarding the availability of zinc for complex interactions. This delivery system showed minor toxicity in normal PNT1A cells and high potency towards PC3 tumor cells. The complex preferentially penetrated PC3 tumor cells in contrast to confinement to the membranes of PNT1A. Furthermore, zinc uptake was confirmed in both cell lines. Molecular analysis was used to confirm the activation of zinc stress (e.g., ZnT-1) and apoptosis (e.g., CASP-1). Our results strongly suggest that the zinc-Schiff base-Novicidin complex has great potential as a novel anticancer drug.

Sarcosine-related amino acids can exceptionally affect the behavior of benign and malignant prostate cells.