NKH477 inhibits proliferation and induces apoptosis in a panel of cancer cell lines

The anti-proliferative effects of cAMP in cancer cells may be regulated by the adenylyl-cyclase-V isoform. As Colforsin Daropate [NKH477] is more selective for this isoform, we hypothesized that this water soluble compound may promise utility as an oral anti-tumour agent. Using separate cancer cell lines [MCF7, HT29, A431, WiDr, RKO, A375, H630, Du145, SW480 and SW620], we studied the effects of NKH477 on cell proliferation, cell viability and apoptosis. NKH477 induced >70% inhibition of proliferation in all cancer cell lines tested. NKH477 induced a dose-dependent apoptosis causing G1 arrest and priming cells to die. NKH477 treatment on the tested cell lines inhibited proliferation and induced apoptosis. Thus, NKH477 shows early promise as an oral anti-cancer agent

Programmed cell death of B lymphocytes is induced by ligation of integrin-associated protein [CD47]

As part of the Immunoglobulin [Ig] superfamily, the transmembrane glycoprotein CD47 forms a signalling complex with the CD23 receptor alphavbeta3 integrin, which stimulates cytokine synthesis and controls inflammation by regulating leukocyte activation and the phagocytosis of aging apoptotic leukocytes. To investigate the effects of anti-CD47 antibodies on a range of cell types at varying stages of development. Using flow cytometric analysis, KMS11 and H929 human B lymphocyte multiple myeloma cell lines were used to study the expression of CD47 and alphavbeta3 integrin as a means to explore the factors relating to the induction and resistance to apoptosis. We found that both cell lines expressed high levels of CD47, with KMS11 cells expressing more than H929 cells. CD47 stimulated an increase in apoptosis in both KMS11 and H929 cells with the preponderance being late apoptotic, dying cells. Ligation of CD47 via the soluble phase was crucial for apoptosis to take place. These results provided an insight into the apoptotic mechanisms involved in the control of inflammation surrounding the activation and phagocytosis of leukocytes. In conclusion, further analysis is required to elucidate the complete signaling cascade responsible for this proliferative effect. Induction of apoptosis via CD47 stimulation appears to occur in the absence of CD47's signaling complex partner, alphavbeta3 whether or not apoptosis occurs, appears to be dependent upon the cell type and also the way CD47 is engaged

Biological activity of bee propolis in health and disease.

Propolis is a natural product derived from plant resins collected by honeybees. It is used by bees as glue, a general-purpose sealer, and as draught-extruder for beehives. Propolis has been used in folk medicine for centuries. It is known that propolis possesses anti-microbial, antioxidative, anti-ulcer and anti-tumor activities. Therefore, propolis has attracted much attention in recent years as a useful or potential substance used in medicine and cosmetics products. Furthermore, it is now extensively used in foods and beverages with the claim that it can maintain or improve human health. The chemical composition of propolis is quite complicated. More than 300 compounds such as polyphenols, phenolic aldehydes, sequiterpene quinines, coumarins, amino acids, steroids and inorganic compounds have been identified in propolis samples. The contents depend on the collecting location, time and plant source. Consequently, biological activities of propolis gathered from different phytogeographical areas and time periods vary greatly. In this review, the activity of bee propolis will be presented with special emphasis on the antitumor activity.

Serum matrix metalloproteinase-9 and tissue inhibitor of 3tetalloproteinase-1 in Egyptian patients with chronic liver disease: correlation with liver fibrosis

Chronic liver disease of different etiologies leads to cirrhosis. The main pathological mechanism of progression to cirrhosis is fibro genesis. Recognition of liver fibrosis or cirrhosis is difficult without liver biopsy. There is an urgent demand for a noninvasive reliable serum marker for liver fibrosis. Alterations in circulating matrix metalloproteinase-9 [MMPs] and tissue inhibitor of metalloproteinase-1 [TIMPs] concentrations and their correlation to the inflammatory activity and the histological changes are fairly well established, thus, the rationale of the present study was to evaluate the relationship between serum MMP-9, and TIMP-1 to liver status in patients with chronic liver disease. This study included 50 patients with chronic liver disease, 18 patients with chronic hepatitis, 22 patients with liver cirrhosis and 10 patients with hepatocellular carcinoma [HCC]. Twenty matched age and sex healthy volunteers were enrolled as control group. The obtained data showed that the lowest serum level of MMP-9 was found in chronic hepatitis patients compared to the control [P<0.05]. The MMP-9 serum level decreased during progression of chronic hepatitis to cirrhosis showing the least level in cirrhotic group. The serum TIMP-1 level was significantly higher in cirrhotic group compared to chronic hepatitis [P<0.05] and control [P<0.001] groups. Serum MMP-9 was negatively correlated to both the TIMP-1 level and to the histological severity of chronic hepatitis. There was a positive correlation between serum TIMP-1 and degree of fibrosis [r= 0.73, P< 0.001]. There were a statistically significant increase of MMP-9 [Pc0.001] and TIMP-l [P

Role of concurrent helicobacter pylori infection to hepatitis C virus in Egyptian patients with liver cirrhosis

Chronic hepatitis C virus [HCV] infection is a leading cause of end-stage liver disease worldwide. It has been shown that helicobacter pylori [H. pylori] plays an important role in chronic gastritis, peptic ulcer disease, and gastric malignancies and its eradication has been advocated. The association between H. pylori infection and cirrhosis in patients with hepatitis C virus was documented in different parts of the world, nevertheless, no conclusive data is available in Egypt In the present study, the status of helicobacter pylori infection was sought in 90 patients with chronic HCV and in 66 HCV free healthy controls. The results showed that the H. pylori positivity was increased significantly [P = 0.03] in the HCV infected patients than of healthy controls where H. pylori infection was found in 50 out of 90 [55.6%] of HCV infected patients versus 26 out of 66 [39.4%] of healthy controls. In HCV infected patients, the incidence of H. pylori infection was increased significantly [P = 0.04] from chronic active hepatitis to cirrhosis. H. pylori was present in 6/18 [33.3%], 10/21[47.6%], 16/27 [59.3%], 18/24 [75.0%] in chronic active hepatitis, Child A, Child B, and Child C respectively. More importantly, the incidence of H. pylori infection in HCV infected patients was increased very significantly [P = 0.003] with increasing of Meld score. The prevalence of H. pylori was documented in 9/28 [32.1%] in patients with Meld score . In conclusion, our results collectively reflect a remarkable increasing of H. pylori prevalence with advancing the hepatic lesions and the eradication treatment may prove beneficial in those patients with chronic hepatitis C

Methanol induced retinal and hepatic toxicity in the rat model and role of antioxidants

Human methanol poisoning is characterized by serious visual impairment, hepatic toxicity and formic acidemia. Non-primate species are resistant to the accumulation of formate and the associated methanol toxicity. A non-primate model of methanol induced toxicity was developed using adult albino rats treated with subanaesthetic concentrations of nitrous oxide to inhibit the oxidation of methanol's toxic metabolites. Methanol intoxicated rats developed retinal and hcpatic toxicity as well as metabolic acidosis analogous to methanol toxicity in humans. This work was conducted on 140 adult albino rats divided into 5 groups. The first group [control group] was further subdivided into 6 subgroups each consisted of 10 rats. The other 4 groups consisted of 20 rats each. Group Ia was the negative control group, group lb received 2 mL normal saline orally, group Ic was exposed to a mixture of N20: 02 [1:1 flow rate 3 liters/min] for 4 hours, group Id was given methyl alcohol orally in a dose of 4 g/kg followed by further 2 doses [2 g/kg] at 12 and 24 hours after the initial dose, group Ie was given N-acetyl cysteine orally in a dose of 100 mg/kg 30 mill and repeated every 8 hours for further 3 doses, and group If was given melatonin orally in a dose of 30 mg/kg 30 min and repeated every 8 hours for further 3 doses. Group II was exposed to N20: 02 mixture for 4 hours followed by methanol administration orally in a dose of 4 g/kg followed by further 2 doses [2 g/kg] at 12 and 24 hours after the initial dose. Group III was exposed to the mixture of N20: 02 for 4 hours then was given methyl alcohol as in group II then N-acetyl cysteine as mentioned before. Group IV was exposed to the mixture of N20: 02 for 4 hours then was given methyl alcohol as in group 11 then melatonin as mentioned before. Group V was exposed to the mixture of N20: O2 for 4 hours then was given methyl alcohol as in group 11 then N-acetyl cysteine and melatonin together in the same doses and timing as groups III and IV. At the end of the experimental period, the animals were anaesthetized for fundus examination. Then the animals were sacrificed, blood samples were withdrawn for measuring arterial blood gases and malondialdehyde [MDA], the eyeballs and livers were taken for histopathological study. The biochemical results revealed highly significant changes in pH, bicarbonate and malondialdehye concentrations in methanol intoxicated rats [group II]. On administration of N-acetyl cysteine or melatonin after methanol intoxication, there was significant decrease in lipid peroxidation products [MDA] especially with melatonin but the pH changes were not improved. As regard to ocular examination there was a significant improvement in optic disc and retinal edema especially when melatonin and N-acetyl cysteine were given together. Histopathological results of the liver and retina revealed an improvement with either N-acetyl cysteine or melatonin, however, melatonin was more protective. The combination of both antioxidants gave the best results. From the results of this study, It can be concluded that melatonin and/or N-acetyl cysteine have protective effects against methanol-induced ocular and hepatic toxicity