Evaluate the Antigenotoxicity and Anticancer Role of β-Sitosterol by Determining Oxidative DNA Damage and the Expression of Phosphorylated Mitogen-activated Protein Kinases', C-fos, C-jun, and Endothelial Growth Factor Receptor.

Abstract

Alterations of EGFR system and MAPKs' play a major role in the development and progression of RCC. In the present study, the blockade of the Fe-NTA promoted EGFR signaling and sustained ERK activity with β-sitosterol leads to impede tumor promotion and maintenance.Rats which are pre-treated with 20 mg/kg bw of β-sitosterol significantly reduced the elevated expression of p-p38 MAPK, p-JNK, p-ERK, c-fos and c-jun in carcinogen induced rats, which suggest that β-sitosterol might protect renal tissue from neoplastic transformation. The interaction of β-sitosterol with the ATP binding site of ERK-2 by molecular docking studies also validates the inhibitory effect of β-sitosterol on ERK-2. The results of the present study reveal that β-sitosterol inhibit oncogenic MAPK signaling, to abrogate hyper cell proliferation, angiogenesis, and to induce apoptosis thereby prevent DEN and Fe-NTA induced renal carcinogenesis. Thus,β-sitosterol that modulates signal transduction pathways and their downstream events may serve as a potential cancer chemopreventive and therapeutic agent. <b>Abbreviation used:</b> AP-1: Activator protein-1,DEPC: Diethyl pyrocarbonate,EDTA: Ethylenediaminetetraacetic acid,EGFR: Endothelial growth factor receptor,ERK: Extracellular-signal regulating kinase,Fe-NTA: Ferric nitrilotriacetate,GAPDH: Glyceraldehyde-3-phosphate dehydrogenase,HBSS: Hank's balanced salt solution,JNK: c-Jun N-terminal kinase,MAPK: Mitogen-activated protein kinase,DEN: N-diethylnitrosamine,RCC: Renal cell carcinoma,SDS-PAGE: Sodium dodecyl sulfate polyacrylamide gel electrophoresis.