Comparative evaluation of the therapeutic strategies using a minimal model of luminal-A breast cancer.

Cellular behavior is heavily influenced by cellular interactions, which are often lost in conventional cell culture methods. As a result, in vitro cellular behavior may not accurately reflect in vivo conditions. Three-dimensional (3D) culture, on the other hand, is better suited for studying cellular behavior as it allows for more comprehensive cell communication. In this study, we utilized 3D culture of the MCF-7 cell line to create a minimal model of luminal-A breast cancer and evaluated its histopathological and morphological features using various methods. To determine the optimal therapeutic strategies for eliminating cancer cells, we assessed the effectiveness of diverse therapeutic approaches, including targeting distinct phases of the cell cycle, endocrine therapy, and gene therapy in both 2D and 3D culture systems. Our findings indicate that cells derived from mammospheres respond differently to their parent cells in monolayer culture depending on the therapeutic strategy used. This variability in drug response may be due to the altered microenvironment created by heterogeneous cellular makeup and emerging cellular interactions in the 3D culture. Therefore, it is important to administer a therapeutic approach that can eradicate cells regardless of the microenvironment.

The effect of caspase-9 in the differentiation of SH-SY5Y cells.

Neuroblastoma is the most common solid malignant tumor in infants and young children. Its origin is the incompletely committed precursor cells from the autonomic nervous system. Neuroblastoma cells are multipotent cells with a high potency of differentiation into the neural cell types. Neural differentiation leads to the treatment of neuroblastoma by halting the cell and tumor growth and consequently its expansion. Caspases are a family of proteins involved in apoptosis and differentiation. The present study aimed to investigate the potential role of caspase-9 activation on the differentiation of the human neuroblastoma SH-SY5Y cells. Here we investigated the caspase-9 and 3/7 activity during 1,25-dihydroxycholecalciferol (D3)-mediated differentiation of SH-SY5Y cells and took advantage of the inducible caspase-9 system in putting out the differentiation of the neuroblastoma cells. D3-induced differentiation of the cells could lead to activation of caspase-9 and caspase-3/7, astrocyte-like morphology, and increased expression of Glial fibrillary acidic protein (GFAP). By using the inducible caspase-9 system, we showed differentiation of SH-SY5Y cells to astrocyte-like morphology and increased level of GFAP expression. Furthered studies using a specific caspase-9 inhibitor showed inhibition of differentiation mediated by D3 or caspase-9 to astrocyte-like cells. These results show the potency of caspase-9 to direct differentiation of the human neuroblastoma SH-SY5Y cells into cells showing an astrocyte-like morphology.

Caspases interplay with kinases and phosphatases to determine cell fate.

Cellular differentiation is one of the critical processes in the life of multicellular organisms. In this phenomenon, a non-specialized cell is converted to a specialized one with its own specific function and morphology. One of the requirements for specialization is silencing of the pathways involved in cell proliferation in parallel with turning on the molecular mechanisms involved in differentiation. Similar to other biological phenomena, the change in cellular state from the proliferative to the differentiated needs molecular switches to persuade the change in response to the internal or external inducers. The quiddity of these molecular switches has not been identified, yet. However, there exists a growing body of evidence showing that the same agents involved in apoptosis have a broad contribution to differentiation progression. To our knowledge, this evidence is still ambiguous because it has raised fundamental questions that require more proof to be answered. The most important questions are: How can two totally different cellular fates act through a similar pathway? What is the separating edge? What forces a cell to choose one of them (death or differentiation)? To address these issues, we will concentrate on three groups of molecules; caspases as the key players of apoptosis, protein kinases, and phosphatases as the major regulators of many cellular and biochemical processes. The evidence reveals a triangle of caspases, kinases, and phosphatases in which their communication leads to the fine-tuning of caspases and consequently they determine cell fate.