Crocin as a novel therapeutic agent against colitis.

Ulcerative colitis is a chronic inflammatory bowel disease with high incidence and prevalence worldwide. To investigate the therapeutic potency of crocin, as a pharmacologically active component of saffron, in dextran sodium sulfate (DSS)-induced colitis mice model. Experimental colitis was induced by 7-day administration of DSS dissolved in water at a concentration of 1.5% (w/v). The animals were randomly divided into four groups (n»6 for each group). (1) Control group received regular drinking water for four weeks, (2) the second group of mice received regular drinking water for three weeks and then received DSS for one week, (3) and (4) the other two groups received 50-ppm or 200-ppm crocin for three weeks, respectively, and then treated with DSS for one week. Our results showed that Crocin attenuates colitis disease activity index including body weight loss, diarrhea, rectal bleeding, and colon shortening in crocin pre-tread mice. Comparison of histology of colon tissues between groups showed that crocin significantly decreases colon histopathological score, at least partially, by eliciting anti-inflammatory responses in DSS-induced colitis mice. These results clearly showed that crocin is a novel therapeutic agent with low toxicity as well as great clinical significance in treatment of colitis.

Phytosomal-curcumin antagonizes cell growth and migration, induced by thrombin through AMP-Kinase in breast cancer.

Here we explored the antitumor-activity of novel-formulated-form of curcumin (phytosomal-encapsulated-curcumin) or in combination with 5-FU in breast cancer. The antiproliferative activity was assessed in 2D and 3-dimensional cell-culture-model. The migratory-behaviors of the cells were determined by migration assay. The expression levels of CyclinD1,GSK3a/b, P-AMPK, MMP9, and E-cadherin were studied by qRT-PCR and/or Western blotting. The anti-inflammatory of nano-curcumin was assessed, while antioxidant activity was evaluated by malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and total thiols (T-SH). To understand dynamic behavior of genes, we reconstructed a Boolean network, while the robustness of this model was evaluated by Hamming distance. phytosomal-curcumin suppressed cell-growth followed by tumor-shrinkage in 3D model through perturbation of AMP-activated protein kinase. Curcumin reduced the invasiveness of MCF-7 through perturbation of E-cadherin. Moreover, phytosomal-curcumin inhibited the tumor growth in xerograph model. Histological staining of tumor tissues revealed vascular disruption and RBC extravasation, necrosis, tumor stroma, and inflammation. Co-treatment of curcumin and 5-FU reduced the lipid-peroxidation and increased MDA/SOD level. Of note, curcumin reduced cyclinD-expression in breast cancer cell treated with thrombin, and activates AMPK in a time-dependent manner. Also suppression of AMPK abrogated inhibitory effect of phytosomal-curcumin on thrombin-induced cyclin D1 over-expression, suggesting that AMPK is essential for anti-proliferative effect of this agent in breast cancer. Our finding demonstrated that phytosomal-curcumin antagonizes cell growth and migration, induced by thrombin through AMP-Kinase in breast cancer, supporting further-investigations on the therapeutic potential of this novel anticancer agent in treatment of breast cancer.

Adenosine: An endogenous mediator in the pathogenesis of gynecological cancer.

Extracellular concentration of adenosine increases in the hypoxic tumor microenvironment. Adenosine signaling regulates apoptosis, angiogenesis, metastasis, and immune suppression in cancer cells. Adenosine-induced cell responses depend upon different subtypes of adenosine receptors activation and type of cancer. Suppression of adenosine signaling via inhibition of adenosine receptors or adenosine generating enzymes including CD39 and CD73 on ovarian or cervical cancer cells is a potentially novel therapeutic approach for gynecological cancer patients. This review summarizes the role of adenosine in the pathogenesis of gynecological cancer for a better understanding and hence a better management of this disease.

Role of adenosine signaling in the pathogenesis of breast cancer.

The plasma level of adenosine increases under ischemic and inflamed conditions in tumor microenvironment. Adenosine elicits a range of signaling pathways in tumors, resulting in either inhibition or enhancement of tumor growth depending upon different subtypes of adenosine receptors activation and type of cancer. Metabolism of adenosine-5'-triphosphate (ATP) and its derivatives including adenosine is dysregulated in the breast tumor microenvironment, supporting the role of this metabolite in the pathogenesis of breast cancer. Adenosine regulates inflammation, apoptosis, cell proliferation, and metastasis in breast cancer cells. This review summarizes the role of adenosine in the pathogenesis of breast cancer for a better understanding and hence a better management of this disease.

Role of Wnt5a in the Pathogenesis of Inflammatory Diseases.

Wnt5a initiates pro-inflammatory responses through activation of non-canonical Wnt signaling pathway. Pro-inflammatory functions of Wnt5a trigger pro-inflammatory signaling cascades and increase secretion of pro-inflammatory cytokines and chemokines. Wnt5a as a potent signaling molecule is strongly implicated in a number of diseases including cancer, diabetes, metabolic disorders, and of special interest in this review, inflammatory diseases. This review summarizes the role of Wnt5a in the pathogenesis of inflammatory diseases including atherosclerosis, rheumatoid arthritis, psoriasis vulgaris and sepsis, promoting greater understanding, and clinical management of these diseases. J. Cell. Physiol. 232: 1611-1616, 2017. © 2016 Wiley Periodicals, Inc.

Proinflammatory signaling functions of thrombin in cancer.

Thrombin-induced activation of protease-activated receptors (PARs) represents a link between inflammation and cancer. Proinflammatory signaling functions of thrombin are associated with several inflammatory diseases including neurodegenerative, cardiovascular, and of special interest in this review cancer. Thrombin-induced inflammatory responses up-regulates expression of cytokines, adhesion molecules, angiogenic factors, and matrix-degrading proteases that facilitate tumor cells proliferation, angiogenesis, invasion, and metastasis. This review summarizes the current knowledge about the mechanisms of thrombin-mediated proinflammatory responses in cancer pathology for a better understanding and hence a better management of this disease.