Ganoderma atrum polysaccharide induces anti-tumor activity via the mitochondrial apoptotic pathway related to activation of host immune response.

Ganoderma atrum polysaccharide (PSG-1), the major active ingredient isolated from Ganoderma atrum, has been suggested as a candidate for cancer therapy. The aim of this study was to investigate the anti-tumor effect of PSG-1 using sarcoma 180 (S-180) transplanted mice and further to examine the molecular mechanisms of PSG-1-induced anti-tumor effect. Results showed that PSG-1 significantly inhibited tumor growth in S-180-bearing mice. PSG-1-induced tumor apoptosis was associated with the alteration of Bcl-2 family proteins, increase of reactive oxygen species generation, loss of mitochondrial membrane potential (Δψ(m) ), release of cytochrome c from the mitochondria into cytosol, and activation of caspase-3 and -9. Elevation of immune function was also shown during PSG-1-induced tumor apoptosis, as evidenced by increase of spleen and thymus indexes, lymphocyte proliferation, concentrations of tumor necrosis factor (TNF)-α, and interleukin-2 in serum. Furthermore, the combined treatment of PSG-1 and cyclophosphamide (CTX) results in an enhancement of the anti-tumor effect of CTX alone via increased host immune response. These results suggested that PSG-1 had a potent anti-tumor activity by induction of tumor apoptosis through mitochondrial pathways, and immunoenhancement effect of PSG-1 was related to its anti-tumor effect. In addition, PSG-1 enhanced CTX-induced anti-tumor activity in S-180-bearing mice.

Li WJ ，Chen Y ，Nie SP ，Xie MY ，He M ，Zhang SS ，Zhu KX ... -  《-》

Enhancement of cyclophosphamide-induced antitumor effect by a novel polysaccharide from Ganoderma atrum in sarcoma 180-bearing mice.

Li W ，Nie S ，Chen Y ，Wang Y ，Li C ，Xie M ... -  《-》

A novel polysaccharide from Ganoderma atrum exerts antitumor activity by activating mitochondria-mediated apoptotic pathway and boosting the immune system.

Zhang S ，Nie S ，Huang D ，Feng Y ，Xie M ... -  《-》

Ganoderma atrum polysaccharide protects cardiomyocytes against anoxia/reoxygenation-induced oxidative stress by mitochondrial pathway.

It is now well established that oxidative stress plays a causative role in the pathogenesis of anoxia/reoxygenation (A/R) injury. Ganoderma atrum polysaccharide (PSG-1), the most abundant component isolated from G. atrum, has been shown to possess potent antioxidant activity. The goals of this study were to investigate the effect of PSG-1 against oxidative stress induced by A/R injury and the possible mechanisms in cardiomyocytes. In this work, primary cultures of neonatal rat cardiomyocytes pretreated with PSG-1 were subjected to A/R and subsequently monitored for cell viability by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The levels of intracellular reactive oxygen species (ROS), apoptosis, and mitochondrial membrane potential (Deltapsi(m)) were determined by flow cytometry. Western blot analysis was used to measure the expression of cytochrome c, Bcl-2 family, and manganese superoxide dismutase (MnSOD) proteins, and the activities of caspase-3 and caspase-9 were determined by a colorimetric method. The results showed that PSG-1 protected against cell death caused by A/R injury in cardiomyocytes. PSG-1 reduced the A/R-induced ROS generation, the loss of mitochondrial membrane potential (Deltapsi(m)), and the release of cytochrome c from the mitochondria into cytosol. PSG-1 inhibited the A/R-stimulated activation of caspase-9 and caspase-3 and alteration of Bcl-2 family proteins. Moreover, PSG-1 significantly increased the protein expression of MnSOD in cardiomyocytes. These findings suggest that PSG-1 significantly attenuates A/R-induced oxidative stress and improves cell survival in cardiomyocytes through mitochondrial pathway.

Li WJ ，Nie SP ，Chen Y ，Xie MY ，He M ，Yu Q ，Yan Y ... -  《-》

Ganoderma atrum polysaccharide evokes antitumor activity via cAMP-PKA mediated apoptotic pathway and down-regulation of Ca(2+)/PKC signal pathway.

Ganoderma atrum polysaccharide (PSG-1) has been commonly suggested as a candidate for prevention and therapy of cancer. We investigated the antitumor effect and the underlying molecular mechanisms of PSG-1. The results showed that PSG-1 inhibited tumor growth and resulted in tumor cell apoptosis in vivo. Here, the data revealed that PSG-1 caused a markedly increase in cAMP and PKA activities, rather than cGMP and PKC. Moreover, the treatment of PSG-1 induced a dramatic increase in the protein level of PKA. In contrast, the expression of PKC and intracellular [Ca(2+)]i were inhibited. Our study also revealed that treatment with PSG-1 increased the spleen and thymus weights, lymphocyte proliferation and macrophage phagocytic activity in tumor-bearing mice. Taken together, we conclude that PSG-1 could inhibit the tumor growth, possibly in part by enhancing the induction of apoptosis through cAMP-PKA signaling pathway and down-regulation of Ca(2+)/PKC signal pathway, activating host immune function in S180-bearing mice.

Zhang S ，Nie S ，Huang D ，Huang J ，Feng Y ，Xie M ... -  《-》