RGDSK:K1 helical rosette nanotube induces apoptosis in human lung carcinoma cells through p38 MAPK cascade

Abstract

Helical rosette nanotubes (HRN) are a novel class of biologically inspired nanotubes that are metal‐free and water‐soluble. To explore the tremendous potential of self‐assembled Arg‐Gly‐Asp‐Ser‐Lys (RGDSK):K1 HRN (1:10 M) for targeted drug delivery, especially into the lung, there is a critical need to understand cellular and molecular actions of these nanotubes. Therefore, we investigated p38 Mitogen‐activated protein kinase (MAPK) cascade, caspase‐3 activity and apoptosis in human lung carcinoma cells (Calu3) exposed to RGDSK:K1 HRN at various concentrations and times. RGDSK:K1 HRN (1:10 μM) induced phosphorylation of a 38 KDa band of p38 MAPK within 5 minutes which was inhibited by MAPK kinase (MEK) inhibitors (PD98059 & U0126; 20 μM). All of the tested concentrations of RGDSK:K1 HRN (1:10 to 40:400 μM) caused a concentration‐dependent increase in Caspase‐3 activity in Calu‐3 cells at 18 hours of the exposure. Highest concentration of RGDSK:K1 HRN (40:400 μM) caused a 10 fold increase in Caspase‐3 activity over the control which was significantly blocked by MEK inhibitor U0126 (20 μM). Flow cytometeric analyses of Calu‐3 cells exposed to RGDSD:K1 and stained with FITC‐Annexin‐V and propidium iodide showed apoptosis in the cells. We conclude that RGDSK:K1 HRN induces p38 MAPK phosphorylation which regulates activation of Caspase‐3 and apoptosis Calu‐3 cells. (NSERC Canada)