Publications by authors named "Agnieszka Bedzinska"
Article Synopsis
- The FAS ligand (FASLG) activates cell death receptors on lymphocytes, but cancer cells usually resist this apoptosis.
- This study reveals that a combination of actinomycin D (ActD) and nutlin-3a (Nut3a) can overcome this resistance by activating pro-apoptotic genes, resulting in over 99% cancer cell death when paired with FASLG.
- The drug combination works by fully activating the p53 pathway, engaging both intrinsic and extrinsic apoptosis mechanisms, and shows less effect on normal human fibroblasts, suggesting a potential advancement in cancer immunotherapy.
Article Synopsis
- p53, a tumor suppressor protein, activates different genes based on its modifications, which vary according to cellular stress levels.
- The combination of actinomycin D and nutlin-3a enhances the phosphorylation of p53 and significantly increases the expression of a gene coding for an obscure phosphatase with two forms, linked to testis and skeletal muscle.
- New findings show that in cancer cells treated with this drug combination, an alternative promoter induces the expression of a specific isoform, TMDP-L1, whose protein product was confirmed via Western blotting across multiple cancer cell lines.
Transcriptomic analyses have revealed hundreds of p53-regulated genes; however, these studies used a limited number of cell lines and p53-activating agents. Therefore, we searched for candidate p53-target genes by employing stress factors and cell lines never before used in a high-throughput search for p53-regulated genes. We performed RNA-Seq on A549 cells exposed to camptothecin, actinomycin D, nutlin-3a, as well as a combination of actinomycin D and nutlin-3a (A + N).
View Article and Find Full Text PDFImmunosenescence in monocytes has been shown to be associated with several biochemical and functional changes, including development of senescence-associated secretory phenotype (SASP), which may be inhibited by klotho protein. To date, it was believed that SASP activation is associated with accumulating DNA damage. However, some literature data suggest that endoplasmic reticulum and Golgi stress pathways may be involved in SASP development.
View Article and Find Full Text PDFIn the previous paper of our group, we have demonstrated that one of the crucial factors involved in the crosstalk between autophagy and apoptosis is klotho protein. We have shown that klotho silencing in normal human fibroblasts intensifies lipopolysaccharide (LPS)-induced p-eIF2a-mediated stress of endoplasmic reticulum and thus leads to retardation of prosurvival autophagy and induction of apoptotic cell death. In this study, we have performed a detailed step-by-step analysis of autophagy flux-related genes' expression and endoplasmic reticulum and Golgi stress related pathways in order to determine the exact mechanistic event when autophagy is inhibited in klotho-deficient cells on account of apoptosis initiation.
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