Aloe-emodin targets multiple signaling pathways by blocking ubiquitin-mediated degradation of DUSP1 in nasopharyngeal carcinoma cells.

Aloe-emodin (AE) has been shown to inhibit the proliferation of several cancer cell lines, including human nasopharyngeal carcinoma (NPC) cell lines. In this study, we confirmed that AE inhibited malignant biological behaviors, including cell viability, abnormal proliferation, apoptosis, and migration of NPC cells. Western blotting analysis revealed that AE upregulated the expression of DUSP1, an endogenous inhibitor of multiple cancer-associated signaling pathways, resulting in blockage of the extracellular signal-regulated kinase (ERK)-1/2, protein kinase B (AKT), and p38-mitogen activated protein kinase（p38-MAPK） signaling pathways in NPC cell lines. Moreover, the selective inhibitor of DUSP1, BCI-hydrochloride, partially reversed the AE-induced cytotoxicity and blocked the aforementioned signaling pathways in NPC cells. In addition, the binding between AE and DUSP1 was predicted via molecular docking analysis using AutoDock-Vina software and further verified via a microscale thermophoresis assay. The binding amino acid residues were adjacent to the predicted ubiquitination site (Lys192) of DUSP1. Immunoprecipitation with the ubiquitin antibody, ubiquitinated DUSP1 was shown to be upregulated by AE. Our findings revealed that AE can stabilize DUSP1 by blocking its ubiquitin-proteasome-mediated degradation and proposed an underlying mechanism by which AE-upregulated DUSP1 may potentially target multiple pathways in NPC cells.

Effects of Side-Chain Engineering with the S Atom in Thieno[3,2-b]thiophene-porphyrin to Obtain Small-Molecule Donor Materials for Organic Solar Cells.

To explore the effect of the introduction of heteroatoms on the properties of porphyrin materials, a new porphyrin-based derivative small-molecule donor named as PorTT-T was designed and synthesized based on alkyl-thieno[3,2-b]thiophene(TT)-substituted porphyrins. The linker bridge and end groups of PorTT-T were the same as those of XLP-II small-molecule donor materials, while the side-chain attached to the core of thieno[3,2-b]thiophene(TT)-substituted porphyrin was different. Measurements of intrinsic properties showed that PorTT-T has wide absorption and appropriate energy levels in the UV-visible range. A comparison of the morphologies of the two materials using atomic force microscopy showed that PorTT-T has a better surface morphology with a smaller root-mean-square roughness, and can present closer intermolecular stacking as compared to XLP-II. The device characterization results showed that PorTT-T with the introduced S atom has a higher open circuit voltage of 0.886 eV, a higher short circuit current of 12.03 mAcm-2, a fill factor of 0.499, a high photovoltaic conversion efficiency of 5.32%, better external quantum efficiency in the UV-visible range, and higher hole mobility.