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Contribution of endoplasmic reticulum stress, MAPK and PI3K/Akt pathways to the apoptotic death induced by a penicillin derivative in melanoma cells
AbstractWe have previously examined the in vitro and in vivo antitumor action of TAP7f, a synthetic triazolylpeptidyl penicillin, on murine melanoma cells. In this work, we explored the signal transduction pathways modulated by TAP7f in murine B16-F0 and human A375 melanoma cells, and the contribution of some intracellular signals to the apoptotic cell death. TAP7f decreased ERK1/2 phosphorylation and increased phospho-p38, phospho-JNK and phospho-Akt levels. ERK1/2 blockage suppressed cell growth, while inhibition of p38, JNK and PI3K-I pathways reduced the antitumor effect of TAP7f. Pharmacological inhibition of p38 and ...
Source: Apoptosis - November 12, 2021 Category: Molecular Biology Source Type: research

Detailed Dissection of UBE3A-Mediated DDI1 Ubiquitination
Discussion Poly-ubiquitinated proteins targeted for degradation might be recognized directly by proteasomal receptors or by proteasomal shuttling proteins. The first shuttling proteins – Ddi1, Rad23 and Dsk2 – were identified and characterized in Saccharomyces cerevisiae (Lambertson et al., 1999; Kaplun et al., 2005). Proteasomal shuttles contain an N-terminal ubiquitin-like (UBL) domain that interacts with the 26S proteasome (Finley, 2009), and a C-terminal ubiquitin-binding domain domain (UBD) that binds to ubiquitin or poly-ubiquitin chains (Bertolaet et al., 2001). When ubiquitinated, substrates are capt...
Source: Frontiers in Physiology - May 2, 2019 Category: Physiology Source Type: research

Human CAR NK Cells: A New Non-viral Method Allowing High Efficient Transfection and Strong Tumor Cell Killing
In conclusion, the method of NK cell transfection described in our present study is highly efficient, does not require expensive dedicated structures necessary for viral transduction and avoids possible risks associated with the use of viral vectors. Importantly, it may be applied to NK cells or NK-92 cell line, greatly improving their anti-tumor activity and providing a new NK cell-based platform for new protocols of adoptive immuno-therapy of cancer. Ethics Statement The Ethical Committee of IRCCS Bambino Gesù Pediatric Hospital approved the study (825/2014). Author Contributions TI designed and performed res...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

NOD2 and TLR2 Signal via TBK1 and PI31 to Direct Cross-Presentation and CD8 T Cell Responses
The objective of this study was to explore the role of NOD2 and TLR2 in cross-presentation in human dendritic cells undertaking an unbiased screen. We have used a quantitative phosphoproteomic analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by a computational analysis to identify the proteins as differentially abundant in response to NOD2 and TLR2 sensing. Validation of the phosphoproteomic analysis was performed by the detection of proteins in phosphoenriched lysates and detected by western blot. Techniques for the modulation of gene expression (shRNA and siRNA) were used to confirm the resu...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

Sanguinarine Induces Apoptosis Pathway in Multiple Myeloma Cell Lines via Inhibition of the JaK2/STAT3 Signaling
In this study, we aimed to investigate the potential anti-proliferative and pro-apoptotic activities of SNG in a panel of MM cell lines (U266, IM9, MM1S, and RPMI-8226). SNG treatment of MM cells resulted in a dose-dependent decrease in cell viability through mitochondrial membrane potential loss and activation of caspase 3, 9, and cleavage of PARP. Pre-treatment of MM cells with a universal caspase inhibitor, Z-VAD-FMK, prevented SNG mediated loss of cell viability, apoptosis, and caspase activation, confirming that SNG-mediated apoptosis is caspase-dependent. The SNG-mediated apoptosis appears to be resulted from suppres...
Source: Frontiers in Oncology - April 16, 2019 Category: Cancer & Oncology Source Type: research