Reishi “Hemlock” Mushrooms (Ganoderma Tsugae)
Ganoderma tsugae Extract Inhibits Growth of HER2-Overexpressing Cancer Cells via Modulation of HER2/PI3K/Akt Signaling Pathway
Ganoderma, also known as Lingzhi or Reishi, has been used for medicinal purposes in Asian countries for centuries. It is a medicinal fungus with a variety of biological properties including immunomodulatory and antitumor activities. In this study, we investigated the molecular mechanisms by which Ganoderma tsugae (GT), one of the most common species of Ganoderma, inhibits the proliferation of HER2-overexpressing cancer cells. Here, we show that a quality assured extract of GT (GTE) inhibited the growth of HER2-overexpressing cancer cells in vitro and in vivo and enhanced the growth-inhibitory effect of antitumor drugs (e.g., taxol and cisplatin) in these cells. We also demonstrate that GTE induced cell cycle arrest by interfering with the HER2/PI3K/Akt signaling pathway. Furthermore, GTE curtailed the expression of the HER2 protein by modulating the transcriptional activity of the HER2 gene and the stability/degradation of the HER2 protein. In conclusion, this study suggests that GTE may be a useful adjuvant therapeutic agent in the treatment of cancer cells that highly express HER2.
In conclusion, we provide a schematic presentation of possible molecular mechanisms in vitro and in vivo for the inhibitory effects of GTE on the proliferation of HER2-overexpressing cancer cells (Figure 6). Our results indicate that GTE induces G1 cell cycle arrest via regulation of the HER2/PI3K/Akt signaling pathway, thereby leading to a reduction in the growth of cancer cells overexpressing HER2. Our data also demonstrate that the depletion of HER2 protein by GTE involves an inhibition in the transcriptional activity of the HER2 gene and an increase in the proteasome-dependent degradation of the HER2 protein. In addition, we have also shown that a combination of GTE with anticancer drugs (e.g., taxol, cisplatin, and doxorubicin) exerts synergistic growth-inhibitory effect on HER2-overexpressing cancer cells. Taken together, our findings suggest that GTE may be a useful and effective adjuvant therapeutic agent for the treatment of cancers that highly express HER2.
Triterpenoids and Polysaccharide Fractions of Ganoderma tsugae Exert Different Effects on Antiallergic Activities
This study was to investigate antiallergic effects of triterpenoids (Gt-TRE) and polysaccharide (Gt-PS) extracts from Ganoderma tsugae, using mast cell line RBL-2H3, T cell line EL4, primary T cells, and transfected RAW264.7 macrophage cells. The results showed that histamine secreted from activated RBL-2H3 mast cells was significantly suppressed by Gt-TRE but not Gt-PS. Interleukin- (IL-) 4 secreted from activated EL4 cells was significantly suppressed by Gt-TRE but not Gt-PS. Further primary CD4+ T cells cultures also confirmed that Gt-TRE (5 ~ 50 µg/mL) significantly suppressed Th2 cytokines IL-4 and IL-5 secretions but had no effect on Th1 cytokines IL-2 and interferon (IFN)-γ. Gt-PS did not affect IL-4 and IL-5 secretions until higher doses (400, 500 µg/mL) and significantly suppressed IFNγ secretions but enhanced IL-2 at these high doses. The reporter gene assay indicated that Gt-TRE inhibited but Gt-PS enhanced the transcriptional activity of NF-κB in activated transfected RAW264.7 cells and transfected EL4 cells. IL-4 secreted by this transfected EL-4 cells was also significantly decreased by Gt-TRE but not by Gt-PS, suggesting that these two fractions may exert different effects on NF-κB related cytokines expression. These data suggested that triterpenoids fraction of Ganoderma tsugae might be the main constituents to alleviate allergic asthma.
In conclusion, triterpenoid extracts of G. tsugae inhibited histamine release from mast cells, Th2 cytokines IL-4, and IL-5 productions in T cells and NF-κB activation but did not affect Th1 cytokines IL-2 and IFNγ secretions. Polysaccharides of G. tsugae activated NF-κB pathway in macrophages and enhanced IL-2 secretion in T cells but did not affect IL-4 production in T cells until high doses. These data demonstrated that triterpenoid extract is the most effective fraction of Ganoderma tsugae that attenuated Th2 response, which is associated with NF-κB transcriptional activity.
Ganoderma tsugae Induces S Phase Arrest and Apoptosis in Doxorubicin-Resistant Lung Adenocarcinoma H23/0.3 Cells via Modulation of the PI3K/Akt Signaling Pathway
Ganoderma tsugae (GT) is a traditional Chinese medicine that exhibits significant antitumor activities against many types of cancer. This study investigated the molecular mechanism by which GT suppresses the growth of doxorubicin-resistant lung adenocarcinoma H23/0.3 cells. Our results reveal that GT inhibits the viability of H23/0.3 cells in vitro and in vivo and sensitizes the growth suppression effect of doxorubicin on H23/0.3 cells. The data also show that GT induces S phase arrest by interfering with the protein expression of cyclin A, cyclin E, CDK2, and CDC25A. Furthermore, GT induces cellular apoptosis via induction of a mitochondria/caspase pathway. In addition, we also demonstrate that the suppression of cell proliferation by GT is through down-regulation of the PI3K/Akt signaling pathway. In conclusion, this study suggests that GT may be a useful adjuvant therapeutic agent in the treatment of lung cancer.
In conclusion, we have demonstrated that GTE induces S phase arrest and the cellular apoptosis of H23/0.3 cells via regulation of the PI3K/Akt signaling pathways (Figure 6(c)). In addition, we have also shown that a combination of GTE and doxorubicin exerts an enhanced growth inhibitory effect on H23/0.3 cells. Our results suggest that GTE may be a safe and effective adjuvant therapeutic agent for the treatment of NSCLC cells with drug resistance.