Antitumor Effect of the Mannich Base(1,3-bis-((3-Hydroxynaphthalen-2-yl)phenylmethyl)urea) on Hepatocellular Carcinoma

Abstract

Abstract:The present study was designed to evaluate the antitumor effects of the synthetic Mannich base 1,3-bis-((3-hydroxynaphthalen-2-yl)phenylmethyl)urea (1,3-BPMU) against HEP-G2 hepatoma cells and diethylnitrosamine (DEN)-induced hepatocarcinoma (HCC) in albino rats. In vitro analysis results revealed that 1,3-BPMU showed significant cytotoxicity and cell growth inhibition in HEP-G2 hepatoma cells in a concentration-dependent manner. Furthermore, flow cytometry results indicated that 1,3-BPMU enhanced early and late apoptosis. The maximum apoptosis was exhibited at a concentration of 100 µg/mL of 1,3-BPMU. In in vivo analysis, DEN treatment increased the content of nucleic acids, LPO and the activities of AST, ALT, ALP, LDH, γGT and 5'NT with decreased antioxidant activity as compared to control rats. However, 1,3-BPMU treatment to DEN-induced rats decreased the content of nucleic acids, LPO and the activities of AST, ALT, ALP, LDH, γGT and 5'NT and increased the activities of SOD, CAT, GPx, GST and GR (p < 0.05). Furthermore, 1,3-BPMU enhanced the apoptosis via upregulation of caspase-3 and caspase-9 and the downregulation of Bcl-2 and Bcl-XL mRNA expression as compared to DEN-induced rats. Histological and ultrastructural investigation showed that 1,3-BPMU treatment renovated the internal architecture of the liver in DEN-induced rats. In this study, the molecular and pre-clinical results obtained by treatment of DEN-induced rats with 1,3-BPMU suggested that 1,3-BPMU might be considered as an antitumor compound in the future.

Effect of co-administration of Bee honey and some chemotherapeutic drugs on dissemination of hepatocellular carcinoma in rats

“…This deterioration may account for the excessive free radicals because of DEN metabolism that caused HCC. In a good agreement with the present findings, Hussain et al [75] ; Zhao et al [120]; Kadasa et al [60]; Chidamabaram et al [121]; Vedarethinam et al [122], investigated that DEN-treated rats showed an unformatted architecture, the presence of inflammatory cells along the central vein and enlarged nuclear size in the liver cells.…”

Evaluation of the antitumor activity of platinum nanoparticles in the treatment of hepatocellular carcinoma induced in rats

“…This study showed significant decrease in Casp-3 level in DEN group compared to normal animals as reported before. 39 Treatment with cis -platin and Pt NPs resulted in increase in Casp-3 level compared to DEN rats. These results are in consonance with previous studies, which indicates that both treatments induced apoptosis as reflected by increase in Casp-3 level.…”

The Curative Effect of Berberine Nanoparticles and Cisplatin Combination Therapies Against Hepatocarcinogenesis-Induced By N-Nitroso-Diethylamine In Male Rat

“…Herein, the high activity of 5 -NT in the DENA-CCl4 intoxicated rats are revealing of intrahepatic obstruction of bile canaliculi as a result of liver cell injury and due to increase in the fluidity of the cell membrane as confirmed by Ghaffar [50]. Moreover, Vedarethinam et al [51] reported that the elevated levels of the 5 -NT marker enzyme in rats injected by DENA are correlated with the malignancy development of DENA action.…”

“…The present results were in the same line of Tawfek et al [58] who stated that induction of DENA-CCl4 caused an elevation in the AFP level, suggesting the occurrence of premalignant liver changes. Similarly, Vedarethinam et al [51] stated that induction of DENA induced liver damage as documented by an increase in AFP.…”