Background:
Cucurbitacin IIb (CIIb) from Ibervillea sonorae has great capacity to suppress the proliferation of cancer cells and induce apoptosis. In this study, the molecular mechanisms related to the antiproliferative and apoptosis induction capacity of CIIb (derivate from Ibervillea sonorae) in HeLa cells was investigated.
Materials and Methods:
By trypan blue exclusion assay the viability and the cell proliferation effect of CIIb was evaluated. The effect of CIIb on the mitochondrial membrane potential was develop by flow cytometry using JC-1. The activity of the caspase-3 and caspase-9 was evaluated through of flow cytometry using commercial kits. By (Fluorescence-Activated Cell Sorting) FACS analysis the effect of CIIb on the cell cycle was investigated. Western blot was used to evaluated the inhibitory effect of CIIb on STAT3 signaling pathway and cyclin –B1as well as DNA damage by comet assay.
Results:
The study of the mechanism of action revealed that CIIb was able to disrupt the mitochondrial membrane potential (ΔΨm) and consequently activate the caspases -3 and -9, how a result of the activation of the intrinsic pathway of the apoptosis. Likewise, CIIb induced cell cycle arrested in S and G2/M after 24h of treatment. CIIb also reduced the expression of STAT3 and cyclin –B1 and finally CIIb induces a great antiproliferative effect at 48 and 72h inducing DNA damage.
Conclusion:
These results demonstrated that CIIb induce apoptosis and cell cycle arrested in HeLa via inhibition of STAT3.
Inside tumors, cancer cells display several mechanisms to create an immunosuppressive environment. On the other hand, by migration processes, mesenchymal stromal cells (MSCs) can be recruited by different cancer tumor types from tissues as distant as bone marrow and contribute to tumor pathogenesis. However, the impact of the immunoregulatory role of MSCs associated with the aggressiveness of breast cancer cells by soluble molecules has not been fully elucidated. Therefore, this in vitro work aimed to study the effect of the conditioned medium of human bone marrow-derived-MSCs (hBM-MSC-cm) on the immunoregulatory capability of MDA-MB-231 and BT-474 breast cancer cells. The hBM-MSC-cm on MDA-MB-231 cells induced the overexpression of TGF-β, IDO, and IL-10 genes. Additionally, immunoregulation assays of mononuclear cells (MNCs) in co-culture with MDA-MB-231 and hBM-MSC-cm decreased lymphocyte proliferation, and increased proteins IL-10, TGF-β, and IDO while also reducing TNF levels, shooting the proportion of regulatory T cells. Conversely, the hBM-MSC-cm did not affect the immunomodulatory capacity of BT-474 cells. Thus, a differential immunoregulatory effect was observed between both representative breast cancer cell lines from different origins. Thus, understanding the immune response in a broader tumor context could help to design therapeutic strategies based on the aggressive behavior of tumor cells.
It is well-known that cardiovascular diseases are the leading cause of death worldwide, and represent an important economic burden to health systems. In an attempt to solve this problem, stem cell therapy has emerged as a therapeutic option. Within the last 20 years, a great variety of stem cells have been used in different myocardial infarction models. Up until now, the use of cardiac stem cells (CSCs) has seemed to be the best option, but the inaccessibility and scarcity of these cells make their use unreliable. Additionally, there is a high risk as they have to be obtained directly from the heart of the patient. Unlike CSCs, adult stem cells originating from bone marrow or adipose tissue, among others, appear to be an attractive option due to their easier accessibility and abundance, but particularly due to the probable existence of cardiac progenitors among their different sub-populations. In this review an analysis is made of the surface markers present in CSCs compared with other adult stem cells. This suggested the pre-existence of cells sharing specific surface markers with CSCs, a predictable immunophenotype present in some cells, although in low proportions, and with a potential of cardiac differentiation that could be similar to CSCs, thus increasing their therapeutic value. This study highlights new perspectives regarding MSCs that would enable some of these sub-populations to be differentiated at cardiac tissue level.
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