Rabbit Anti-Human FASLG (C-terminal) Polyclonal antibody

The rosette nanotubes (RNTs) are a class of biologically inspired, self-assembling, metal-free, hydrophilic nanotubes, which hold tremendous potential as targeted drug delivery vehicles. We investigated the cell signaling events caused by lysine-functionalized RNTs (K-RNT) co-assembled with Arg-Gly-Asp-Ser-Lys-functionalized RNTs (RGDSK-RNT) for induction of inflammation and apoptosis in human adenocarcinoma (Calu-3) cells. When co-assembled in a ratio of 1:10 mu M these composite RNTs (referred to as RGDSK/K-RNTs) rapidly induced phosphorylation of P38 mitogen-activated protein kinase (MAPK) within 2 min. Higher concentrations of RGDSK/K-RNTs (>10:100 mu M) resulted in a P38 MAPK-dependent increase in secretion of TNF-alpha. RGDSK/K-RNTs (1:10-40:400 mu M) also caused a concentration- and P38 MAPK-dependent increase in caspase-3 activity and DNA fragmentation in Calu-3 cells at 18 h of exposure. Over-expression of pro-apoptotic genes including caspase-3, BAK1, CIDEB, TP53BP2, FAS, TNF and FASLG supported pro-apoptotic behaviors of these RNTs. We conclude that RGDSK/K-RNTs induce phosphorylation of P38 MAPK, which regulate secretion of TNF-alpha, activation of caspase-3 and apoptosis in Calu-3 cells. These results suggest that the RNTs could be used as a drug to induce apoptosis in cancer cells or as a versatile platform to deliver a variety of biologically active molecules for cancer therapy. (C) 2009 Elsevier Ltd. All rights reserved.

Background. In this study, we aimed to determine synergistic apoptotic and cytotoxic effects of methylstat and bortezomib on U266 and ARH77 multiple myeloma (MM) cells. Methods. Cytotoxic effects of the drugs were demonstrated by MTT cell proliferation assay while apoptotic effects were examined by loss of mitochondrial membrane potential (MMP) by JC-1 MMP detection kit, changes in caspase-3 enzyme activity and Annexin-V apoptosis assay by flow cytometry. Expression levels of apoptotic and antiapoptotic genes were examined by qRT-PCR. Results. Our results showed that combination of methylstat and bortezomib have synergistic antiproliferative effect on MM cells as compared to either agent alone. These results were also confirmed by showing synergistic apoptotic effects determined by increased loss of mitochondrial membrane potential and increased caspase-3 enzyme activity and relocation of phosphotidyleserine on the cell membrane by Annexin-V/PI double staining. Combination of bortezomib with methylstat arrested cells at the S phase of the cell cycle. Methylstat treatment caused upregulation of FASLG, NGFR, TNF, TNI-RS10B and TNFRS1B apoptotic genes and downregulation of AKT1, AVEN, BAG1 BCL2L2 and RELA antiapoptotic genes in a dose and time dependent manner. Conclusion. In conclusion, our data suggested that bortezomib in combination with methylstat decreased cell proliferation and induced apoptosis significantly in U266 and ARH77 cells. When supported with in vivo analyses, methylstat might be considered as a potential new agent for the treatment of MM. (C) 2020 IMSS. Published by Elsevier Inc.