Antagonism byGanoderma lucidumPolysaccharides Against the Suppression by Culture Supernatants of B16F10 Melanoma Cells on Macrophage

Abstract

It is well-documented that macrophages have the functions to regulate antitumor immune response. Antitumor response can be launched by a series of events, starting with inflammation mediated by monocyte/macrophages, which stimulates natural killer and dendritic cells and finally activates the cytotoxic lymphoid system. Monocytes/macrophages may be the first line of defense in tumors. However, specific and nonspecific immunotherapy for human cancer has shown no success or limited success in clinical trials. Part of the reasons attribute to tumor-derived soluble factors that suppress functions of immune cells or induce apoptosis of these cells, including macrophages. Therefore, antagonism of the suppression on the macrophages is an important goal for tumor immunotherapy. To achieve this purpose, Ganoderma lucidum polysaccharides (Gl-PS) with multiple bioactivities were used on mouse peritoneal macrophages incubating with culture supernatants of B16F10 melanoma cells (B16F10-CS). It was shown that the viability, phagocytic activity, NO production, TNF-α production and activity in peritoneal macrophages after activation by lipopolysaccharide were suppressed by B16F10-CS, while the suppressions were fully or partially antagonized by Gl-PS. In conclusion, B16F10-CS is suppressive to the viability, phagocytic activity, NO production, TNF-α production and activity in peritoneal macrophages while Gl-PS had the antagonistic effects against this suppression, suggesting this potential of Gl-PS to facilitate cancer immunotherapy.

Carbohydrates Against Cancer

“…Polysaccharides from Ganoderma lucidum (mainly ganoderans, a type of β-glucans) and Cordyseps sinensis (mainly α-glucans including WIPS and the more potent polysaccharide, AIPS) could inhibit proliferation of tumor cells by stimulating the production of cytokines by activation of mononuclear cells (Liu et al 2004;Giavasis 2014;Lu et al 2014). The effective fractions of polysaccharidepeptides/proteins from G. lucidum have also indicated anti-angiogenesis, immunomodulatory (and also prevention of immunosuppression caused by cyclophosphamide), anti-adhesion of tumor cells, and induction of cell apoptosis in cancerous cells even stronger than PSP in some cases (Pang et al 2007).…”

“…It is demonstrated that the mechanism of anticancer/antitumor action of most polysaccharides involves nonspecific immunomodulation that leads to activation of macrophages, production of cytokines (including interleukins and tumor necrosis factor) and improving host defense, which ends in eliminating tumor cells (Zhang et al 2014;Chang 2007;Popa 2011;Lu et al 2014). The other major mechanism is to counter the effects of mutated tumor suppressor gene p53.…”

Ganoderma lucidum for Cancer Treatment

“…62 Moreover, Gl-PS antagonizes the suppression induced by culture supernatant of melanoma cells on viability, nitric oxide (NO) production, phagocytic activity, tumor necrosis factor alpha (TNF-α) production, and activity of peritoneal macrophages. 63 Guo et al 64 extracted a water-soluble polysaccharide (GSG) from the spores of G. lucidum and suggested that it can effectively induce IL-6 and TNF-α secretion in murine resident peritoneal macrophages, which is partially mediated by the glucan receptor, Dectin-1, and MAPKs-and Syk-dependent pathway. On the other hand, immunomodulating activity of GLP was demonstrated by the reduction of IL-6 and TNF-α levels and increased concentration of IL-2, IL-4, and IL-10 in serum of rats with gastric cancer.…”

Triterpene-loaded microemulsion using Coix lacryma-jobi seed extract as oil phase for enhanced antitumor efficacy: preparation and in vivo evaluation

“…In view of its complex components, most research groups have explored the antitumor effect of G. lucidum by using specific extracts of the plant, eg, triterpene, which has demonstrated cytotoxicity against cancer cells, in preference to total extracts, which may have a more comprehensive but weaker physiologic effect. [7][8][9][10] Likewise, adlay seed oil, extracted from adlay using supercritical CO 2 , has been used in the treatment of cancer for a number of years. However, due to the particularly low solubility and poor permeability of triterpene and adlay seed oil, the Ling-Yi formulation still presents several challenges because of its unacceptable biopharmaceutical performance.…”