epiglucan and Ovarian-Neoplasms

Ovarian cancer is a lethal type of cancer which is initiated to the ovaries and affects 1 out of every 75 women. Due to the high number of deaths (almost 152,000) related to this cancer, it seems that novel efficient therapeutic methods are required in this field. Beta-glucans are a type of glucose linear polymers which have been proven to have a lot of advantageous activities. Recently, investigations have declared that these polysaccharides have the potential to be used as anti-cancer drugs. These agents are able to affect several mechanisms such as inflammation and apoptosis, and that is how cancers are prone to be affected by them. In this review, we attempt to investigate the role of beta-glucans on ovarian cancer. We hope that this paper would give some novel insights into the field of ovarian cancer treatment.

Topics: Antineoplastic Agents; Apoptosis; beta-Glucans; Carcinoma, Ovarian Epithelial; Female; Humans; Ovarian Neoplasms

Topics: Antineoplastic Agents; beta-Glucans; Carbohydrate Sequence; Female; Humans; Ovarian Neoplasms; Pleurotus; Solubility; Tumor Cells, Cultured

Two sulfated derivatives (PRP-S1 and PRP-S2) of a β-glucan from Phellinus ribis with different degrees of substitution were obtained by chlorosulfonic acid method. The derivatives could block formation of new vessels in zebrafish and inhibit the proliferation of human umbilical vein endothelial cells (HUVECs). The two sulfated derivatives had remarkably high antitumor activities in vivo (in BALB/c mice inoculated with H22 hepatocellular carcinoma) as well as in vitro (against human ovary cancer SKOV-3 cells), without producing any overt signs of general toxicity. The results of immunohistochemistry assay indicated that the derivatives significantly reduced the average number of microvessel density (MVD) and inhibited the expression of vascular endothelial growth factor (VEGF) in tumor. Thus, these derivatives exhibit pronounced antiangiogenic and antitumoral properties. Except for cytotoxic effects on tumor cells, it is reasonable to expect that the antitumoral effects of PRP-S1 and PRP-S2 are mediated via their antiangiogenic properties.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Basidiomycota; beta-Glucans; Carbohydrate Sequence; Carcinoma, Hepatocellular; Cell Proliferation; Cells, Cultured; Female; Glucans; Human Umbilical Vein Endothelial Cells; Humans; Immunoenzyme Techniques; Liver Neoplasms; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Neovascularization, Pathologic; Ovarian Neoplasms; Xenograft Model Antitumor Assays; Zebrafish

Administration of a combination of yeast-derived beta-glucan with antitumor monoclonal antibodies (mAb) has significant therapeutic efficacy in a variety of syngeneic murine tumor models. We have now tested this strategy using human carcinomas implanted in immunocompromised severe combined immunodeficient mice. Combined immunotherapy was therapeutically effective in vivo against NCI-H23 human non-small-cell lung carcinomas, but this modality was surprisingly ineffective against SKOV-3 human ovarian carcinomas. Whereas NCI-H23 tumors responded to this combination therapy with increased intratumoral neutrophil infiltration and C5a production, these responses were lacking in treated SKOV-3 tumors. Further results suggested that SKOV-3 tumors were protected by up-regulation of the membrane complement regulatory protein CD55 (decay-accelerating factor). Blockade of CD55 in vitro led to enhanced deposition of C activation product C3b and increased cytotoxicity mediated by beta-glucan-primed neutrophils. In vivo, administration of anti-CD55 mAb along with beta-glucan and anti-Her-2/neu mAb caused tumor regression and greatly improved long-term survival in animals bearing the previously resistant SKOV-3 tumors. This was accompanied by increased intratumoral neutrophil accumulation and C5a production. We conclude that CD55 suppresses tumor killing by antitumor mAb plus beta-glucan therapy (and, perhaps, in other circumstances). These results suggest a critical role for CD55 to regulate iC3b and C5a release and in turn to influence the recruitment of beta-glucan-primed neutrophils eliciting killing activity.

Topics: Animals; Antibodies, Monoclonal; beta-Glucans; Carcinoma, Non-Small-Cell Lung; CD55 Antigens; Cell Line, Tumor; Chemotaxis, Leukocyte; Complement C3a; Complement C5a; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Mice; Mice, Inbred ICR; Mice, SCID; Neutrophil Infiltration; Ovarian Neoplasms; Saccharomyces cerevisiae; Tumor Cells, Cultured

The Basidiomycete fungus Agaricus blazei Murill has traditionally been used as a health food for the prevention of cancer.. We examined whether beta-(1-6)-D: -glucan extracted from A. blazei is a potential anticancer agent in an in vitro and in vivo animal model.. Here we show that (1) beta-glucan had cytotoxic effect against human ovarian cancer HRA cells, but not against murine Lewis lung cancer 3LL cells, in vitro; (2) beta-glucan promotes p38 MAPK activity for suppressing HRA cell proliferation and amplifying the apoptosis cascade; (3) beta-glucan stimulates translocation of the proapoptotic protein, Bax, from the cytosol to mitochondria, cytochrome c release, and subsequent caspase-9 activation; (4) treatment with SB203580, a p38 MAPK-specific inhibitor, suppresses beta-glucan-induced effects, indicating that activation of p38 MAPK is involved in the suppression of cell proliferation and mitochondrial activation-mediated cell death pathway; (5) in mice, oral supplementation with beta-glucan reduces pulmonary metastasis of 3LL cells and peritoneal disseminated metastasis of HRA cells and inhibits the growth of these metastatic tumors in lung or peritoneal cavity, in part, by suppressing uPA expression; and (6) in an in vivo experimental metastasis assay, however, the oral supplementation with beta-glucan after i.v. tumor cell inoculation did not reduce the number of lung tumor colonies.. Treatment with beta-glucan may be beneficial for cancer patients with or at risk for metastasis. The beta-glucan-dependent signaling pathways are critical for our understanding of anticancer events and development of cancer therapeutic agents.

Topics: Administration, Oral; Agaricus; Animals; Antineoplastic Agents; Apoptosis; beta-Glucans; Carcinoma, Lewis Lung; Cell Proliferation; Drug Administration Schedule; Enzyme Activation; Female; Humans; Mice; Ovarian Neoplasms; p38 Mitogen-Activated Protein Kinases; Peritoneal Neoplasms; Signal Transduction; Tumor Cells, Cultured