Journal: International Journal of Molecular Sciences

Article Title: Activation of ERK and p38 Reduces AZD8055-Mediated Inhibition of Protein Synthesis in Hepatocellular Carcinoma HepG2 Cell Line

doi: 10.3390/ijms222111824

Figure Lengend Snippet: Screening anticancer drugs for identification of translation inhibitors. ( a , b ) The level of translation in mouse embryonic fibroblasts (MEFs) was measured using puromycin incorporation assay. Polypeptide chains in wild-type MEFs treated with 10 μM ( a ) or the indicated concentrations ( b ) of Selleck Anti-cancer Compound Library for 24 h were labeled with puromycin for 10 min. The number of cells (left column) and Alexa Fluor 488 intensities of each area (right column) were assessed using Operetta High-Content analysis system. Operetta images were analyzed using Harmony software. Red dots in the red dotted circle in B indicate MEFs treated with various concentrations of AZD8055. To recognize the shape of cells, cells were stained with Hoechst 33342 prior to the measurement of cytoplasmic Alexa Fluor 488 intensities. The number of compounds include DMSO- and Tg-treated samples. ( c – e ) Wild-type (S/S) or eIF2α mutant (A/A) MEFs were treated with the indicated concentrations of AZD8055 for 24 h; two representative confocal images are shown ( c ). The intensity of Alexa Fluor 488 was visualized ( c ) and MEFs treated with various concentrations of AZD8055 were magnified ( c ). Scale bar = 200 μM. The obtained images were measured using Harmony Software ( d ). Immunoblot analyses were performed to determine the relative amount of puromycin and phosphorylated form of eIF2α using specific antibodies for puromycin, eIF2α, phosphorylated form of eIF2α (p-eIF2α), and GAPDH ( e ). Treatment with thapsigargin (Tg), an ER stress inducer, was used as a positive control. Fold changes in d were calculated by comparing DMSO control group of each cell line with AZD8055 treatment groups. Statistically significant differences were determined by Student’s t -test and were indicated as *** p < 0.001.

Article Snippet: The cells were treated with dimethyl sulfoxide (DMSO; Biosesang, Korea) or Selleck Anti-Cancer Compound Library for 24 h. Cells treated with 1 µM Tg for 30 min served as positive control.

Techniques: Labeling, High Content Screening, Software, Staining, Mutagenesis, Western Blot, Positive Control

Journal: Molecules

Article Title: Stress Granule Core Protein-Derived Peptides Inhibit Assembly of Stress Granules and Improve Sorafenib Sensitivity in Cancer Cells

doi: 10.3390/molecules29092134

Figure Lengend Snippet: Overexpression of SIP fragments blocks the formation of SGs induced by sorafenib. ( A ) Screen for SG-inducing anticancer compounds. HeLa cells stably expressing GFP-G3BP2 were treated with 10 μM compounds (geldanamycin, vinorelbine, and ceritinib) or 50 μM sorafenib for 2 h and captured for fluorescent images. ( B ) Immunofluorescence showing that overexpression of SIP fragments effectively inhibited sorafenib-induced SGs. HeLa cells were transfected with indicated expression plasmids, treated with 50 μM sorafenib for 2 h and subjected to immunofluorescence staining using the anti-G3BP1 antibody. Empty triangles indicate cells without SGs. Scale bars: 20 µm. ( C ) Statistical analysis of SG induction efficiency shown in panel ( B ), which is reflected by the percentage of SG-positive cells among cells successfully transfected with expression plasmids. * p ≤ 0.05.

Article Snippet: A total of 244 compounds from the anticancer compound library (APExBIO, Shanghai, China) were used to carry out a screen for SG-inducing anticancer compounds.

Techniques: Over Expression, Stable Transfection, Expressing, Immunofluorescence, Transfection, Staining

Journal: Molecules

Article Title: Stress Granule Core Protein-Derived Peptides Inhibit Assembly of Stress Granules and Improve Sorafenib Sensitivity in Cancer Cells

doi: 10.3390/molecules29092134

Figure Lengend Snippet: Working model of SIPs that increase the efficacy of sorafenib in cancer cells. Sorafenib imposes stress on cancer cells, which respond to induce SGs that promote stress adaptation and cell survival. SIP-C1/2 and SIP-U1 derived from SG core proteins Caprin1 and USP10 exert a dominant effect and USP10-mimic effect on the SG-promoting function of G3BP1, leading to inhibition on SG assembly and cell survival. Combined treatment of SG-inducing anticancer drugs with SIPs might alleviate SG-associated drug resistance.

Article Snippet: A total of 244 compounds from the anticancer compound library (APExBIO, Shanghai, China) were used to carry out a screen for SG-inducing anticancer compounds.

Techniques: Derivative Assay, Inhibition

Journal: Pharmaceuticals

Article Title: Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

doi: 10.3390/ph14070626

Figure Lengend Snippet: Clinical trials in GB targeting the vascular endothelial growth factor receptor.

Article Snippet: Regorafenib (BAY73-4506, Stivarga, Bayer HealthCare Pharmaceuticals Inc., Leverkuzen, Germany), which targets both membrane receptors (VEGFR, PDGFR, c-KIT, RET) and intracellular kinases (Raf, BRAF), is an oral multi-kinase inhibitor developed by Bayer which targets angiogenic, stromal and oncogenic receptor tyrosine kinase.

Techniques: Clinical Proteomics

Journal: Pharmaceuticals

Article Title: Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

doi: 10.3390/ph14070626

Figure Lengend Snippet: Clinical trials in GB targeting the platelet-derived growth factor receptor.

Article Snippet: Regorafenib (BAY73-4506, Stivarga, Bayer HealthCare Pharmaceuticals Inc., Leverkuzen, Germany), which targets both membrane receptors (VEGFR, PDGFR, c-KIT, RET) and intracellular kinases (Raf, BRAF), is an oral multi-kinase inhibitor developed by Bayer which targets angiogenic, stromal and oncogenic receptor tyrosine kinase.

Techniques: Clinical Proteomics

Journal: Pharmaceuticals

Article Title: Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

doi: 10.3390/ph14070626

Figure Lengend Snippet: Clinical trials in GB targeting the fibroblast growth factor receptor.

Article Snippet: Regorafenib (BAY73-4506, Stivarga, Bayer HealthCare Pharmaceuticals Inc., Leverkuzen, Germany), which targets both membrane receptors (VEGFR, PDGFR, c-KIT, RET) and intracellular kinases (Raf, BRAF), is an oral multi-kinase inhibitor developed by Bayer which targets angiogenic, stromal and oncogenic receptor tyrosine kinase.

Techniques: Clinical Proteomics

Journal: Pharmaceuticals

Article Title: Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

doi: 10.3390/ph14070626

Figure Lengend Snippet: Clinical trials on single agent multi-kinase inhibitors for GB therapy.

Article Snippet: Regorafenib (BAY73-4506, Stivarga, Bayer HealthCare Pharmaceuticals Inc., Leverkuzen, Germany), which targets both membrane receptors (VEGFR, PDGFR, c-KIT, RET) and intracellular kinases (Raf, BRAF), is an oral multi-kinase inhibitor developed by Bayer which targets angiogenic, stromal and oncogenic receptor tyrosine kinase.

Techniques: Clinical Proteomics