Studies on anticancer activity of 1 3 bis 3 hydroxy naphthalen 2yl phenyl methyl urea on hepatocellular carcinoma in wistar albino rats

Abstract

ABSTRACT newline newline newlineThe present study is designed to evaluate the chemo-therapeutic effect of synthetic mannich base-1,3-Bis-[(3-hydroxy-naphthalen-2-yl)-phenyl-methyl]- urea(1,3BPMU)against HEP-G2 hepatoma cell line and DEN induced hepatocarcinoma (HCC) in albino rat. In-vitro analysis of 1,3BPMU show significant cytotoxicity and cell growth inhibition in HEP-G2 hepatoma cell line at the concentration of 50 and#956;g/ml and 100 and#956;g/ml in all the 3 days. In addition, Flow cytometry analysis was also carried out, maximum necrosis (21.1%), late apoptosis (7.5%) and early apoptosis (1.0%) were observed at a concentration of 100 and#956;g/ml. Results of In-vivo analysis reveals that, increased DNA , RNA and LPO, activities of markers enzymes such as Aspartate transferase (AST), Alanine transferase (ALT), Alkaline phosphatase(ALP), Lactate dedehydrigenase(LDH), Gamma glutamyl transferase(and#947;GT), 5 -Nucleotidase (5 NT) and decreased activity of antioxidant status such as Super oxide dismutase(SOD), Catalse(CAT), Glutathione peroxidase(GPx), Glutathione-S-transferase(GST), Glutathione reductase(GR) were observed in DEN-induced cancer rats. The administration of 1,3BPMU significantly reversed the altered levels of DNA and RNA, cancer marker proteins, LPO, liver marker and antioxidant status as compared with DEN induced rats. Further, DEN treatment up regulates the Bcl-2 and Bcl-XL and down regulates Cas-3 and Cas- newline9mRNA transcripts level as compared with control rats. The rats treated with newline newline1,3BPMU significantly reversed the altered apoptotic and antiapoptotic gene expression. Hematoxylin and eosin (HE) staining and TEM evaluation show irregular and abnormal nucleus in DEN-induced rats, after cancer rats treated with newline1, 3BPMU significantly induced the apoptosis. To understand the basics of proteins and its role in HCC we used proteomic analysis. Two Dimensional polyacrylamide gel electrophoresis and Matrix-Assisted Laser Desorption/Ionisation-Time of Flight Mass Spectrometry (MALDI