The burden of cancer diseases is increasing every year, therefore, the demands to figure out novel drugs that can retain antitumor properties have been raised. This study aimed to investigate the anti-tumor properties of amygdalin (Amy) against Ehrlich ascites carcinoma (EAC) bearing mice and its protective properties against liver damage. Amy and the standard anticancer drug Sorafenib (Sor) were given alone or in combination to Swiss albino female mice that had been injected with EAC cells. Biochemical parameters of liver function (AST, ALT, GGT, total protein, albumin), tumor volume, oxidative stress [malondialdehyde, (MDA)] and antioxidative [superoxide dismutase (SOD), and reduced glutathione (GSH)] markers were measured. The hepatic expression of the antioxidant-related gene [nuclear factor erythroid-2-related factor 2 (Nrf2)], the migration-related gene [matrix metalloprotease 9 (MMP9)], and the angiogenesis-related gene [vascular endothelial growth factor (VEGF)] were evaluated by qPCR. The results revealed that EAC-bearing mice treated with Amy and/or Sor showed a decrease in the tumor burden and hepatic damage as evidenced by (1) decreased tumor volume, number of viable tumor cells; (2) increased number of dead tumor cells; (3) restored the liver function parameters; (4) reduced hepatic MDA levels; (5) enhanced hepatic GSH and SOD levels; (6) upregulated expression of Nrf2; (7) downregulated expression of MMP9 and VEGF, and (8) improved hepatic structure. Among all treatments, mice co-treated with Amy (orally) and Sor (intraperitoneally) showed the best effect. With these results, we concluded that the Amy improved the antitumor effect of Sor and had a protective role on liver damage induced by EAC in mice.

Background Traditional herbal medicine has been used for centuries to cure many pathological disorders, including cancer. Thymoquinone (TQ) and piperine (PIP) are major bioactive constituents of the black seed (Nigella sativa) and black pepper (Piper nigrum), respectively. The current study aimed to explore the potential chemo-modulatory effects, mechanisms of action, molecular targets, and binding interactions after TQ and PIP treatments and their combination with sorafenib (SOR) against human triple-negative breast cancer (MDA-MB-231) and liver cancer (HepG2) cells. Methods We determined drug cytotoxicity by MTT assay, cell cycle, and death mechanism by flow cytometry. Besides, the potential effect of TQ, PIP, and SOR treatment on genome methylation and acetylation by determination of DNA methyltransferase (DNMT3B), histone deacetylase (HDAC3) and miRNA-29c expression levels. Finally, a molecular docking study was performed to propose potential mechanisms of action and binding affinity of TQ, PIP, and SOR with DNMT3B and HDAC3. Results Collectively, our data show that combinations of TQ and/or PIP with SOR have significantly enhanced the SOR anti-proliferative and cytotoxic effects depending on the dose and cell line by enhancing G2/M phase arrest, inducing apoptosis, downregulation of DNMT3B and HDAC3 expression and upregulation of the tumor suppressor, miRNA-29c. Finally, the molecular docking study has identified strong interactions between SOR, PIP, and TQ with DNMT3B and HDAC3, inhibiting their normal oncogenic activities and leading to growth arrest and cell death. Conclusion This study reported TQ and PIP as enhancers of the antiproliferative and cytotoxic effects of SOR and addressed the mechanisms, and identified molecular targets involved in their action.

Hyperhomocysteineamia (hHcys) is thought to be a risk factor for cardiovascular disease. The epigenetic (protein) pattern due to the effect of hHcys in kidney and liver was profiled in the supplemented developing rats. A group treated with 0.6 % Hcys for 8 weeks and trimethylglycine (Tri or Betaine) antioxidant treated group (6 g / Kg) were compared with four weeks age control group. The results indicated that, a great variety in protein pattern was obtained. Specific type of protein with M.W. of 214.29 K. d. was produced in the kidney samples treated with Trimethylglycine. Common types of protein with M.

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The radio-protective role of fenugreek (fen) and IFN was studied against the damage effects induced by gamma irradiation in liver of albino rats. Male and female albino rats were paired. The produced generations were separated into 3 classes PC, PT& P-ir, representing untreated, fed with standard food mixed with 5% Fen seed powder (FSP) and exposed to whole body irradiation (WBI) respectively. Animals were allowed for mating to give F 1. F 1 was separated into 3 subgroups (ir-ir), (ir+FSP) and (ir-IFN), subjected to another dose of irradiation, fed with standard food mixed with FSP, injected with IFN respectively. All individuals were arranged for pairing until the production of F 2. DNA assay was carried out using RAPD-PCR fingerprinting technique. Six arbitrary primers were used. They produced various numbers of fractions ranging between zero to 8 within each of the studied groups. Some specific fractions were picked out indicating polymorphic alleles. Quantitative mutations were observed within the percentage area of the generated bands. Highest and / or lowest similarity indices were observed between the studied groups indicating complementary to the used primer or pointing to some degree or to complete disturbance in the DNA sequencing as a result of the different treatments. In conclusion the remarked changes in DNA fingerprinting confirmed the potential transmission of radiation damage of genome to the progeny while each of fen and IFN ameliorated the harmful effects of irradiation.