The role of RGD-tagged helical rosette nanotubes in the induction of inflammation and apoptosis in human lung adenocarcinoma cells through the P38 MAPK pathway

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• 作者：Sarabjeet S. Suri ; Felaniaina Rakotondradany ; Andrew J. Myles ; Hicham Fenniri ; Baljit Singh
• 关键词：Cell signaling ; Apoptosis ; P38 MAPK ; TNF-α ; DNA fragmentation ; Caspase-3
• 刊名：Biomaterials
• 出版年：2009
• 出版时间：June 2009
• 年：2009
• 卷：30
• 期：17
• 页码：3084-3090
• 全文大小：580 K

文摘

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 μM 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 μM) resulted in a P38 MAPK-dependent increase in secretion of TNF-α. RGDSK/K-RNTs (1:10–40:400 μM) 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-α, 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.