Manganese as a Possible Anticancer Enhancer in Docetaxel Treatment of Prostate Cancer Cells.

BACKGROUND/AIM: Treatment of castration-resistant prostate cancer with docetaxel (DOC) often leads to resistance. In this study, we investigated whether manganese (Mn) has the potential to enhance treatment when combined with DOC. MATERIALS AND METHODS: PC3 cells were exposed to DOC or Mn individually and in combination and cell viability was analysed in a dose- and time-dependent manner. Cell toxicity, cell cycle analysis and apoptotic protein levels were determined after 48 h of treatment. RESULTS: Mn in combination with different concentrations of DOC significantly enhanced the inhibitory effect on cell viability. Although the lowest dose did not cause mitotic arrest, DOC increased toxicity, which was reduced when combined with Mn. Protein analyses indicated that Mn compensates for the suppression of death receptors when combined with a low concentration of DOC and induced non-apoptotic pathways when combined with a higher concentration. CONCLUSION: Combining DOC and Mn may allow for a reduction in DOC concentration with the potential to reduce side effects.

Cell Biology of the Tardigrades: Current Knowledge and Perspectives.

The invertebrate phylum Tardigrada has received much attention for containing species adapted to the most challenging environmental conditions where an ability to survive complete desiccation or freezing in a cryptobiotic state is necessary for persistence. Although research on tardigrades has a long history, the last decade has seen a dramatic increase in molecular biological ("omics") studies, most of them with the aim to reveal the biochemical mechanisms behind desiccation tolerance of tardigrades. Several other aspects of tardigrade cell biology have been studied, and we review some of them, including karyology, embryology, the role of storage cells, and the question of whether tardigrades are eutelic animals. We also review some of the theories about how anhydrobiotic organisms are able to maintain cell integrity under dry conditions, and our current knowledge on the role of vitrification and DNA protection and repair. Many aspects of tardigrade stress tolerance have relevance for human medicine, and the first transfers of tardigrade stress genes to human cells have now appeared. We expect this field to develop rapidly in the coming years, as more genomic information becomes available. However, many basic cell biological aspects remain to be investigated, such as immunology, cell cycle kinetics, cell metabolism, and culturing of tardigrade cells. Such development will be necessary to allow tardigrades to move from a nonmodel organism position to a true model organism with interesting associations with the current models C. elegans and D. melanogaster.

Manganese Inhibits Viability of Prostate Cancer Cells.

BACKGROUND/AIM: Androgen deprivation therapy is usually in the initial phase a successful treatment for prostate cancer but eventually most patients develop androgen-independent metastatic disease. This study investigated if manganese (Mn) reduces viability of prostate cancer via induction of apoptosis. MATERIALS AND METHODS: The prostate cancer cell lines PC3, DU145 and LNCaP underwent dose- and time-dependent screening of viability, analyzed by the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. Flow cytometry was used for the cell-cycle and apoptosis analyses. Intracellular Mn concentration was measured using inductively coupled plasma-mass spectrometry. RESULTS: At Mn concentrations of 200-1000 µM, the effect on viability was most pronounced in PC3 followed by LNCaP cells. These cell lines also showed higher intracellular concentration of Mn compared to DU145. In all cell lines, Mn increased the proportion of cells arrested in the G0/G1 phase and induced apoptosis. CONCLUSION: To our knowledge, this is the first report demonstrating Mn as a potential agent in prostate cancer therapy.