Polysaccharide K induces Mn superoxide dismutase (Mn-SOD) in tumor tissues and inhibits malignant progression of QR-32 tumor cells: possible roles of interferon α, tumor necrosis factor α and transforming growth factor β in Mn-SOD induction by polysaccharide K

Abstract

Previously we reported the malignant progression of QR-32, a regressor-type tumor clone, following co-implantation with foreign bodies (gelatin sponge or plastic plate) in normal syngeneic C57BL/6 mice. We also reported that the progression of QR-32 cells by a gelatin sponge was significantly inhibited in the mice administered polysaccharide K (PSK) and that PSK induced an increase of radical scavengers, especially manganese superoxide dismutase (Mn-SOD), locally at the site of tumor tissues. In this study, to reveal the possible mechanism by which PSK induced Mn-SOD in the tumor tissues, we examined the mRNA expression and protein levels of inflammatory cytokines in the tissues. We found that mRNAs of tumor necrosis factor alpha (TNFalpha) and interleukin-1alpha (IL-1alpha) were considerably expressed in both PSK-treated and phosphate-buffered-saline-treated tumors, and that the mRNA expression and protein level of interferon gamma (IFNgamma) increased in the tumor tissues treated with PSK. In vitro treatment of QR-32 cells with IFNgamma did not significantly increase the production of Mn-SOD; however, the combination of IFNgamma with TNFalpha increased the Mn-SOD production more effectively than did any of the cytokines used singly. Furthermore, we observed the down-regulation of the mRNA expression and protein level of transforming growth factor beta (TGFbeta) in the tumor tissues treated with PSK, and that in vitro treatment of QR-32 cells with TGFbeta decreased the production of Mn-SOD. These results suggest that PSK suppresses the progression of QR-32 cells by increasing Mn-SOD via the modulation of inflammatory cytokines; that is, by decreasing TGF-beta and increasing IFN-gamma.

Role of host angiotensin II type 1 receptor in tumor angiogenesis and growth

“…We used a mouse model of tumor angiogenesis as described previously (17). We employed two different cell lines, B16-F1 melanoma and QRsP-11 fibrosarcoma cells, which can grow in the C57BL/6 strain mouse (17,18). B16-F1 melanoma cells (batch no.…”

Beyond foreign‐body‐induced carcinogenesis: Impact of reactive oxygen species derived from inflammatory cells in tumorigenic conversion and tumor progression

“…In other words, foreign-body-induced carcinogenesis in QR cells will be prevented if the cells have an adequate amount of antioxidative enzymes or induction of the enzymes at the implantation site. The prevention was actually achieved by induction of Mn-SOD at the coimplantation site by administering Mn-SOD-inducible biological response modifier 109 or orally available superoxide dismutase in this system. 110 Moreover, it is assumed that RNS are partially involved in the model, because administration of a broad inhibitor for inducible nitric oxide significantly inhibited inflammation-induced tumor progression.…”

Protein-bound polysaccharide-K reduces colitic tumors and improves survival of inflammatory bowel disease in vivo

“…PSK has been reported to induce cytokine production, and to be associated with the expression of cytokines, including interleukin (IL)-1, 2, 4, 6, 8 and 10, tumor necrosis factor (TNF)-α, and transforming growth factor-β (18)(19)(20)(21). However, the significance of these findings in vivo has yet to be clarified.…”