Hepatocellular carcinoma is a major health problem worldwide especially in Egypt. It accounts for the fifth common cancer and the second cause of death among different cancers. This study investigated the efficacy and molecular mechanism of Nisin and/or Thioridazine as anticancer treatment on human liver cancer HepG2 cell line. Nisin and Thioridazine were applied for 24 h on human liver cancer cell line (HepG2). 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was done to assess the cytotoxicity of Nisin and Thioridazine. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used for the assessment of PI3K, AKT, SIRT-1, and NRF2 expression in the treated cell line. The protein level of reactive oxygen species (ROS) and vascular endothelial growth factor (VEGF) was measured in the collected media by ELISA technique. Western blot analysis was done for, tAKT, pAKT, tPI3K, and pPI3K. Cell proliferation results showed that compared with the untreated cancer, Nisin and/or Thioridazine treated groups had decreased cell proliferation (p value< 0.0001). Nisin and/or Thioridazine decreased PI3K/AKT mRNA and protein expression in hepatocellular carcinoma cells (HCC). Also Nisin and/or Thioridazine decreased anti-oxidative SIRT1/NRF2 mRNA expression. ROS level highly increased with Nisin and/or Thioridazine treatment in contrast to VEGF protein level which was highly decreased. These results introduce Nisin and Thioridazine as new therapeutic lines in HCC.

Objective: The present work investigated the protective effect of Ficus carica (common fig) leaves methanol extract against genotoxicity and testicular damage of cisplatin (CP) and identified some of its active ingredients. Methods: Seven main groups were investigated as follows: I. control negative, II. Control plant (600 mg/kg fig, orally), III, IV. Control positive (treated i.p with 10 and 15 mg/kg CP), V-VII. groups treated with fig (200, 400 and 600 mg/ kg) + Cisplatin (15 mg/kg). Results: Ficus carica alleviated the destructive effects of CP in the testis, liver and bone marrow due to the presence of high amount of flavonoids and phenolic compounds. Also it has a normal effect in the tested parameters as compared with the control negative. Chromatographic investigation resulted in the identification of 6 compounds: Catechin, Luteolin-8-C-β-D glucopyranoside, Quercetin, Quercetin-3-O-β-d-glucopyranoside, Chlorogenic acid and Kaempferol-3-O-β-D-glucopyranoside. In bone marrow cisplatin induced significant percentage of chromosome abnormalities, micronuclei in polychromatic erythrocytes and toxicity to cells. On the contrary the two tested doses of cisplatin had a normal effect on spermatocyte chromosomes (germ cells). The dose 15 mg/kg induced an overexpression of the liver genes NF-kB and iNOS as indicated by real-time PCR. Different forms of histopathological alterations and instigation of the expression of TNF-α gene in the testis were detected after CP treatment. Conclusion: Ficus carica is a promising candidate rich in many bioactive constituents and can be used in combination with chemotherapeutic drugs to alleviate their destructive effects.

Introduction: Hepatitis C virus (HCV) infection results in chronic hepatitis in more than 70% of infected patients, while 20-30% of patients recover spontaneously. This strengthens the role of the host genetic factors in either spontaneous or drug-induced viral clearance. The aim of this study was to investigate the relationship between interleukin-1β +3953 gene polymorphism and the response to interferon therapy in chronic HCV patients infected with genotype 4. Methodology: The interleukin-1β (+3953 C/T) (rs1143634) gene was amplified in 115 chronic HCV patients. Interleukin-1β single nucleotide polymorphism (SNP) plus several clinical and pathological factors were statistically analyzed in correlation with response to therapy. Results: Genotypes C/T and T/T had a significant association with non-response to treatment compared to genotype C/C, which had a strong association with response to treatment (95% confidence; 6.4884-48.5818, p = 0.0001). Furthermore, analysis of allele frequency in this cohort revealed that the T allele is associated with non-response, higher fibrosis, and higher hepatic activity, while the C allele had a significant association with sustained virologic response lower fibrosis, and lower hepatic activity (p value = 0.0001). Conclusion: This is the first study to examine the correlation between interleukin-1β (+3953 C/T) (rs1143634) gene polymorphism and the response of interferon therapy in genotype 4 HCV-infected patients. The results encourage further assessment of this SNP as a marker to predict response to therapy and disease progression, which can have major implications in saving money, time, and in avoiding unnecessary adverse effects.