Evaluation of small-molecule modulators of the circadian clock: promising therapeutic approach to cancer.

The circadian clock is an important regulator of human homeostasis. Circadian rhythms are closely related to cell fate because they are necessary for regulating the cell cycle, cellular proliferation, and apoptosis. Clock dysfunction can result in the development of diseases such as cancer. Although certain tumors have been shown to have a malfunctioning clock, which may affect prognosis or treatment, this has been postulated but not proven in many types of cancer. Recently, important information has emerged about the basic characteristics that underpin the overt circadian rhythm and its influence on physiological outputs. This information implies that the circadian rhythm may be managed by using particular small molecules. Small-molecule clock modulators target clock components or different physiological pathways that influence the clock. Identifying new small-molecule modulators will improve our understanding of critical regulatory nodes in the circadian network and cancer. Pharmacological manipulation of the clock may be valuable for treating cancer. The discoveries of small-molecule clock modulators and their possible application in cancer treatment are examined in this review.

Evaluation of kinetic effects of Gliotoxin in different breast cancer cell lines.

In the present research, the antiproliferative properties of Gliotoxin, which is obtained from marine fungus and thought to be a promising metabolite, on MCF-7 and MDA-MB-231 breast cancer cells, which have different molecular subtypes, were evaluated. Different cell kinetic parameters were employed for this aim. In experiments, cell viability, cell index, mitotic index, BrdU labeling index, and apoptotic index were assessed. Gliotoxin concentrations of 1.5625 µM, 3.125 µM, and 6.25 µM were used in studies for both cell lines. As a result of the values obtained from cell viability and xCELLigence Real-Time Cell Analysis (RTCA) System, 1.5625 µM concentration was determined as IC50 dose. This concentration was applied to all other parameters and anticancer activities were observed.

N-acetylcysteine attenuates sodium arsenite-induced oxidative stress and apoptosis in embryonic fibroblast cells.

In recent years, the increase in environmental pollutants has been one of the most important factors threatening human and environmental health. Arsenic, a naturally occurring element found in soil, water, and air, easily enters the human body and leads to many metabolic disorders. In this study, we focused on the possible protective effects of N-acetylcysteine (NAC) against sodium arsenite (As)-induced toxic effects on embryonic fibroblast cells. The effects of As and NAC treatment on cells were evaluated, including cytotoxicity, oxidative stress, and apoptosis. Embryonic fibroblast cells were exposed to As (ranging from 0.01 µM to 10 µM) and NAC (at a concentration of 2 mM) for 24 h. The assessment of cytotoxicity markers, such as cell viability and lactate dehydrogenase (LDH), showed that As significantly reduced cell viability and increased LDH levels. Furthermore, we observed that As increased the amount of reactive oxygen species (ROS) in the cell, decreased the activity of antioxidant enzymes, and triggered apoptosis in cells. Additionally, our research revealed that the administration of NAC mitigates the detrimental effects of As. The results showed that As exerted hazardous effects on embryonic fibroblast cells through the induction of oxidative stress and apoptosis. In this context, our study provides evidence that NAC may have a protective effect against the toxicity of As in embryonic fibroblast cells.

The use of hyaluronic acid in a 3D biomimetic scaffold supports spheroid formation and the culture of cancer stem cells.

Three-dimensional (3D) bioprinting culture models capable of reproducing the pathological architecture of diseases are increasingly advancing. In this study, 3D scaffolds were created using extrusion-based bioprinting method with alginate, gelatin, and hyaluronic acid to investigate the effects of hyaluronic acid on the physical properties of the bioscaffold as well as on the formation of liver cancer spheroids. Conformational analysis, rheological characterization, and swelling-degradation tests were performed to characterize the scaffolds. After generating spheroids from hepatocellular carcinoma cells on the 3D scaffolds, cell viability and proliferation assays were performed. Flow cytometry and immunofluorescence microscopy were used into examine the expression of albumin, CD44, and E-cadherin to demonstrate functional capability and maturation levels of the spheroid-forming cells. The results show that hyaluronic acid in the scaffolds correlates with spheroid formation and provides high survival rates. It is also associated with an increase in CD44 expression and a decrease in E-cadherin, while there is no significant change in the albumin expression in the cells. Overall, the findings demonstrate that hyaluronic acid in a 3D hydrogel scaffold supports spheroid formation and may induce stemness. We present a promising 3D scaffold model for enhancing liver cancer spheroid formation and mimicking solid tumors. This model also has the potential for further studies to examine stem cell properties in 3D models.