Chemopreventive activities of Trigonella foenum graecum (Fenugreek) against breast cancer

Cancer is the second leading cause of death worldwide. Conventional therapies cause serious side effects and, at best, merely extend the patient's lifespan by a few years. Cancer control may therefore benefit from the potential that resides in alternative therapies. There is thus an increasing demand to utilize alternative concepts or approaches to the prevention of cancer. In this report, we show a potential protective effect of Fenugreek seeds against 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced breast cancer in rats. At 200 mg/kg b.wt., Fenugreek seeds' extract significantly inhibited the DMBA-induced mammary hyperplasia and decreased its incidence. Epidemiological studies also implicate apoptosis as a mechanism that might mediate the Fenugreek's anti-breast cancer protective effects. To our knowledge, this is the first study that suggests significant chemopreventive effects of Fenugreek seeds against breast cancer.     

Tyrosine phosphatase inhibition induces an ASC-dependent pyroptosis

Macrophage migration inhibitory factor (MIF) is known to contribute to the pathogenesis of inflammatory hyperalgesia and neuropathic pain. Prior studies have shown that Vitamin E treatment is associated with attenuated hyperalgesia and reduced neuropathic pain in rodents. Given these observations, we investigated the possibility that Vitamin E is a MIF inhibitor. Dopachrome tautomerase assays revealed that Vitamin E inhibits the enzymatic activity of purified human recombinant MIF (rhMIF) in a dose-dependent manner (45%, 74%, 92% and 100% inhibition at 3, 10, 30 and 100μM, respectively). Cell-free ELISA based assays showed that Vitamin E binds onto rhMIF thereby blocking its recognition (48% inhibition at 100μM). Circular dichroism studies indicated the Vitamin E has a strong affinity to bind to rhMIF (binding constant 19.52±1.4μM). In silico studies demonstrated that Vitamin E docks well in the active site of MIF with the long aliphatic chain of Vitamin E exhibiting strong van der Waals interactions with MIF. Most importantly, human cell-based assays revealed that Vitamin E significantly inhibits rhMIF-induced production of pro-inflammatory cytokines in a dose-dependent manner (77%, 80%, and 96% inhibition of IL-6 production, respectively, at 10, 30 and 100μM). Taken together, these results demonstrate that Vitamin E inhibits not only the enzymatic activity of MIF but more importantly the biological function of MIF. Our findings suggest that Vitamin E may be attenuating hyperalgesia and reducing neuropathic pain at least in part by inhibiting MIF activity.     

Monocyte Caspase-1 Is Released in a Stable,Active High Molecular Weight Complex Distinct from the Unstable Cell Lysate-Activated Caspase-1

Mononuclear phagocytes utilize caspase-1 activation as a means to respond to danger signals. Although caspase-1 was discovered using highly concentrated cell extracts that spontaneously activate caspase-1, it is now clear that in live cell models caspase-1 activation occurs in the process of its cellular release and is not an intracellular event. Therefore, we compared the characteristics of caspase-1 activation in the cell lysate model to that of caspase-1 that is released in response to exogenous inflammasome activation. Whereas both models generated active caspase-1, the cell-lysate induced caspase-1 required highly concentrated cell lysates and had a short half-life (~15 min) whereas, the activation induced released caspase-1 required 2–3 log fold fewer cells and was stable for greater than 12 h. Both forms were able to cleave proIL-1beta but unexpectedly, the released activity was unable to be immunodepleted by caspase-1 antibodies. Size exclusion chromatography identified two antigenic forms of p20 caspase-1 in the activation induced released caspase-1: one at the predicted size of tetrameric, p20/p10 caspase-1 and the other at >200 kDa. However, only the high molecular weight form had stable functional activity. These results suggest that released caspase-1 exists in a unique complex that is functionally stable and protected from immunodepletion whereas cell-extract generated active caspase-1 is rapidly inhibited in the cytosolic milieu.     

The significance of Epstein Barr Virus (EBV) & DNA Topoisomerase II alpha (DNA-Topo II alpha) immunoreactivity in normal oral mucosa, Oral Epithelial Dysplasia (OED) and Oral Squamous Cell Carcinoma (OSCC)

Background

The glycosylation of a great number of molecules, glyco-protein or glycolipids, has been of interest for decades.

Objective

To compare the expressive patterns of the isoantigenic determinants of histo-blood groups ABH and Lewis in squamous and simple epithelium and in precursors and cancers of the cervix.

Methods

A total of 36 lesions and neoplasms (10 LG-SIL, 16 HG-SIL and 10 invasive carcinomas) have been studied with immunohistochemical techniques, using monoclonal antibodies (MoAb BG1 to BG8) for precursor chains, blood-group ABH and Lewis group Le^a, Le^b, Le^x, and Le^y, and four types of lectins. In addition, we have studied the expression of p53 protein and PCNA, establishing the rate of proliferation of each lesion. Using PCR techniques, we have also detected part of the intron of the E6 gene of HPV-16.

Results

In the invasive cervical carcinomas, we observed a loss of expression of the Le^x antigen (p < 0.01). With regard to the progression of the different lesions studied, we found alterations in the patterns of expression of the antigens of the ABH and Lewis blood groups. There was a tendency towards a loss of expression and heterogeneous patterns in the more advanced lesions, as well as over-expression of the Le^y antigens. With PCNA, we established a proliferative rate which tended to be greater in relation to the progression of the cervix neoplasms.

Conclusion

These results indicate that there is a relation between the losses of histo-blood groups and the progression of the squamous intraepithelial lesions.