Tannic acid attenuate AKT phosphorylation to inhibit UMUC3 bladder cancer cell proliferation.

Urothelial bladder cancer is rapidly spreading across Western countries, and therapy has shown little-to-moderate effects on bladder cancer. Thus, focusing on curbing cancer incidence has become crucial. The aim of the present study was to investigate the anticancer effects of Tannic acid (TA) in human bladder cancer. UMUC3 bladder cancer cells were treated with different concentrations of TA (0-100 µM) and tested for cell viability, colony formation, and apoptosis. The involvement of the phosphoinositide-3 kinase (PI3K)/Akt pathway in the action of TA was examined. TA treatment significantly inhibited the viability and increased percentage of apoptotic cells, thereby decreasing antiapoptotic proteins (BCL2, MCL-1, and BCL-XL) expression, resulting in the Caspase-3 activation. TA treatment decreased stem cell markers expression such as SOX2, OCT4, and NANOG. Additionally, TA treatment significantly reduced the phosphorylation levels of Akt in bladder cancer cells. Our study demonstrates the growth inhibitory effects of TA in bladder cancer cells, and highlights its potential as an anticancer agent for bladder cancer.

Urolithins impair cell proliferation, arrest the cell cycle and induce apoptosis in UMUC3 bladder cancer cells.

Ellagitannins have been gaining attention as potential anticancer molecules. However, the low bioavailability of ellagitannins and their extensive metabolization in the gastrointestinal tract into ellagic acid and urolithins suggest that the health benefits of consuming ellagitannins rely on the direct effects of their metabolites. Recently, chemopreventive and chemotherapeutic activities were ascribed to urolithins. Nonetheless, there is still a need to screen and evaluate the selectivity of these molecules and to elucidate their cellular mechanisms of action. Therefore, this work focused on the antiproliferative effects of urolithins A, B and C and ellagic acid on different human tumor cell lines. The evaluation of cell viability and the determination of the half-maximal inhibitory concentrations indicated that the sensitivity to the studied urolithins varied markedly between the different cell lines, with the bladder cancer cells (UMUC3) being the most susceptible. In UMUC3 cells, urolithin A was the most active molecule, promoting cell cycle arrest at the G2/M checkpoint, increasing apoptotic cell death and inhibiting PI3K/Akt and MAPK signaling. Overall, the present study emphasizes the chemopreventive/chemotherapeutic potential of urolithins, highlighting the stronger effects of urolithin A and its potential to target transitional bladder cancer cells.

Single-Molecule Telomere Assay via Optical Mapping (SMTA-OM) Can Potentially Define the ALT Positivity of Cancer.

Telomeres play an essential role in protecting the ends of linear chromosomes and maintaining the integrity of the human genome. One of the key hallmarks of cancers is their replicative immortality. As many as 85-90% of cancers activate the expression of telomerase (TEL+) as the telomere maintenance mechanism (TMM), and 10-15% of cancers utilize the homology-dependent repair (HDR)-based Alternative Lengthening of Telomere (ALT+) pathway. Here, we performed statistical analysis of our previously reported telomere profiling results from Single Molecule Telomere Assay via Optical Mapping (SMTA-OM), which is capable of quantifying individual telomeres from single molecules across all chromosomes. By comparing the telomeric features from SMTA-OM in TEL+ and ALT+ cancer cells, we demonstrated that ALT+ cancer cells display certain unique telomeric profiles, including increased fusions/internal telomere-like sequence (ITS+), fusions/internal telomere-like sequence loss (ITS-), telomere-free ends (TFE), super-long telomeres, and telomere length heterogeneity, compared to TEL+ cancer cells. Therefore, we propose that ALT+ cancer cells can be differentiated from TEL+ cancer cells using the SMTA-OM readouts as biomarkers. In addition, we observed variations in SMTA-OM readouts between different ALT+ cell lines that may potentially be used as biomarkers for discerning subtypes of ALT+ cancer and monitoring the response to cancer therapy.

Methacrylated chitosan as a polymer with enhanced mucoadhesive properties for transmucosal drug delivery.

Chitosan is a cationic polysaccharide that exhibits mucoadhesive properties which allow it to adhere to mucosal tissues. In this work, we explored chemical modification of chitosan through its reaction with methacrylic anhydride to synthesise methacrylated derivative with the aim to improve its mucoadhesive properties. The reaction products were characterised using 1H NMR, FTIR and UV-Vis spectroscopy. 1H NMR and ninhydrin test were used to quantify the degree of methacrylation of chitosan. Turbidimetric analysis of the effect of pH on aqueous solubility of the polymers revealed that the highly methacrylated derivative remained turbid and its turbidity did not change from pH 3 to 9. However, solutions of native chitosan and its derivative with low methacrylation remained transparent at pH 6.5 and exhibited a rapid increase in turbidity at pH > 6.5. The mucoadhesive properties of chitosan and its methacrylated derivatives were evaluated using flow-through method combined with fluorescent microscopy with fluorescein sodium as a model drug. The retention of these polymers was evaluated on porcine bladder mucosa in vitro. The methacrylated derivatives exhibited greater ability to retain fluorescein sodium on the bladder mucosa compared to the parent chitosan. Toxicological studies using MTT assay with UMUC3 bladder cells show no significant differences in toxicity between chitosan and its methacrylated derivatives suggesting good biocompatibility of these novel mucoadhesive polymers.