DEPTOR is an endogenous inhibitor of mTOR complexes, de-regulated in cancers. The present study reveals a vital role for DEPTOR in survival of cervical squamous cell carcinoma (SCC). DEPTOR was found to be overexpressed in both cervical SCC cells and tissues and it's silencing in cervical SCC cells induced apoptosis, mainly by up-regulation of p38 MAPK and by inhibiting PI3K/AKT pathway via a feed-back inhibition from mTORC1-S6K. DEPTOR silencing resulted in reduced expression of the nitric oxide synthases iNOS and eNOS, as well as increased activation of ERK1/2 and p38 MAP kinases. Activation of AKT signaling by overexpression of constitutively active-AKT (CA-AKT) failed to overcome the apoptosis caused by DEPTOR silencing. Similarly pharmacological inhibition of ERK also failed to control apoptosis. However pharmacological inhibition of p38 MAPK rescued the cells from apoptosis, indicating the major role of p38 MAPK in cell death induced by DEPTOR silencing. DEPTOR was also found to regulate ERK1/2 in an AKT dependent manner. DEPTOR knockdown induced cell death in SiHa cells overexpressing the anti-apoptotic Bcl-2 and Bcl-xL, indicating strong survival role of DEPTOR in these cells. DEPTOR overexpression activated PI3K/AKT by relieving the negative feed-back inhibition from mTORC1-S6K. DEPTOR regulation was also observed to be independent of HPV E6/E7 oncoproteins, but it might be a molecular co-factor contributing to cervical carcinogenesis. In summary, DEPTOR is found to promote survival of cervical SCC cells and its reduction induced apoptosis via differential effects on PI3K/AKT and p38 MAPK and can be a potential target in cervical SCC.
Background: In vivo angiogenesis is normal and vital process in growth and development, wound healing, and formation of granulation tissue wherein new blood vessels form from preexisting vessels as part of revascularization. Platelet-rich products promote wound healing associated with angiogenesis. Biomaterials such as titanium were found to be angiogenic. Unlike in vivo situations, in vitro angiogenesis, study cells, within a controlled environment. Aims: The aim of this study is to evaluate the angiogenic potential of a novel platelet-rich product. Materials and Methods: Blood was drawn from volunteers with informed consent. Blood samples were centrifuged to obtain platelet-rich products. Platelet concentrates prepared were platelet-rich plasma (PRP), platelet-rich fibrin, and a novel platelet-rich product which is titanium-prepared PRP (TPRP), obtained using titanium. The study which compared platelet concentrate was divided into four groups subjected to tissue culture. Phase-contrast microscope was used to determine the rate of growth by cell counting. Statistical Analysis: ANOVA was used for comparison within groups and post hoc for multiple comparisons. Results: TPRP group showed granular ground substance. Group with platelet-rich fibrin (PRF) shows a high rate of growth whereas those with TPRP showed better growth rate when compared to its counterpart, PRP. Conclusions: This is the first study which introduces TPRP. Previous studies have proved that titanium-prepared PRF has better structural quality than its counterpart platelet-rich fibrin. This study concludes that TPRP has better angiogenic potential than its counterpart PRP. Further in vivo studies are needed to promote TPRP as a new generation of platelet products.
Breast cancer is second most common in women and accounts for 23% of all occurring cancers in women. Patients with breast cancer have increasingly shown resistance and high toxicity to chemotherapeutic drugs. Plant-derived products have proved to be an important source of anti-cancer drugs. The present study was to investigate the anti cancer activity of ethanolic extract of Trachyspermum ammi against MCF-7 cell lines. The preliminary phytochemical studies of ethanolic extract of Trachyspermum ammi showed the presence of flavanoids, alkaloids, glycosides, steroids, carbohydrates, phenols, tannins and terpenes. The IC50 concentration of ethanolic extract of Trachyspermum ammi was determined by MTT assay. The results showed the greater degree of cytotoxicity at the dose of 25µg/ml of Trachyspermum ammi and it has been taken as IC50 value for our further study. Then, we also evaluated the apoptotic effect by measuring the morphological changes, cell viability rates using light and fluorescent microscopical studies and DNA fragmentation by using gel electrophoresis method. The ethanolic extract of Trachyspermum ammi showed significant signs of apoptosis such as cell shrinkage, membrane blebbing and nuclei DNA fragmentation. Further, we analyze the gene expression mRNA levels by using RT-PCR method, it showed the expression of p53 was significantly (P<0.001) increased when compared with normal MCF-7 cell line. The expression of anti apoptotic gene Bcl-2 was significantly (P<0.01) reduced when compared with MCF-7 cell line. From this study we conclude that ethanolic extract of Trachyspermum ammi having significant anticancer activity against MCF-7 cell lines and it might be good therapeutic value for further investigation to develop natural compounds as a anti tumor agents.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.