PMID: 

Nutrients. 2019 May 19 ;11(5). Epub 2019 May 19. PMID: 31109134

Abstract Title: 

Extract Reduces the Motility of Breast Cancer Cells Mediated by the RAC⁻Lamellipodin Axis.

Abstract: 

Breast cancer (BC) is the second leading cause of cancer death among women worldwide. The main cause of BC morbidity and mortality is the invasiveness capacity of cancer cells that may lead to metastasis. Here, we aimed to investigate the therapeutic efficacy ofextract (GLE)-a medicinal mushroom with anticancer properties-on BC motility via the Rac/Lamellipodin pathway. GLE treatment effects were tested on MDA-MB-231 breast cancer cells. The effects were tested on cell viability, migration and invasion. Pulldowns, immunoblotting, and immunofluorescence were used to measure Rac activity and the expression of proteins involved in cell migration and in lamellipodia formation, respectively. As a result, GLE suppressed BC cell viability, migration, and invasion capacity. GLE impaired Rac activity, as well as downregulated Lamellipodin, ENA/VASP, p-FAK (Tyr925), Cdc42, and c-Myc expression. Lamellipodia formation was significantly reduced by GLE. In conclusion, we demonstrate that GLE reduces Rac activity and downregulates signaling molecules involved in lamellipodia formation. These novel findings serve as basis for further studies to elucidate the potential of GLE as a therapeutic agent regulating the Rac/Lamellipodin pathway in BC metastasis.

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PMID: 

Cell Death Dis. 2019 Jun 11 ;10(6):456. Epub 2019 Jun 11. PMID: 31186406

Abstract Title: 

Autophagic flux disruption contributes to Ganoderma lucidum polysaccharide-induced apoptosis in human colorectal cancer cells via MAPK/ERK activation.

Abstract: 

Targeting autophagy may serve as a promising strategy for cancer therapy. Ganoderma lucidum polysaccharide (GLP) has been shown to exert promising anti-cancer effects. However, the underlying mechanisms remain elusive. Whether GLP regulates autophagy in cancer has never been reported. In this study, GLP induced the initiation of autophagy in colorectal cancer (CRC) HT-29 and HCT116 cells, as evidenced by enhanced level of LC3-II protein, GFP-LC3 puncta, and increased formation of double membrane vacuoles. However, GLP treatment caused marked increase of p62 expression. Addition of late stage autophagy inhibitor, chloroquine (CQ), further enhanced LC3-II and p62 level, as well as increased autophagosome accumulation, suggesting a blockage of autophagic flux by GLP in CRC cells. We then found GLP blocked autophagosome and lysosome fusion as determined by mRFP-GFP-LC3 colocalization analysis. Mechanistic study revealed that GLP-induced disruption of autophagosome-lysosome fusion is due to reduced lysosome acidification and lysosomal cathepsin activities. Cell viability and flow cytometry assays revealed that GLP-induced autophagosome accumulation is responsible for GLP-induced apoptosis in CRC cells. In line with this, inhibition of autophagy initiation by 3-methyladenine (3-MA), an early stage autophagy inhibitor, attenuated GLP-induced apoptosis. In contrast, suppression of autophagy at late stage by CQ enhanced the anti-cancer effect of GLP. Furthermore, we demonstrated that GLP-induced autophagosome accumulation and apoptosis is mediated via MAPK/ERK activation. Finally, GLP inhibited tumor growth and also inhibited autophagic flux in vivo. These results unveil new molecular mechanism underlying anti-cancer effects of GLP, suggesting that GLP is a potent autophagy inhibitor and might be useful in anticancer therapy.

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PMID: 

Environ Sci Pollut Res Int. 2019 Aug ;26(23):23967-23980. Epub 2019 Jun 20. PMID: 31222655

Abstract Title: 

Protective effects of Ganoderma lucidum triterpenoids on oxidative stress and apoptosis in the spleen of chickens induced by cadmium.

Abstract: 

Cadmium (Cd) is a heavy metal that poses a huge potential threat to human and animal health. Therefore, it is necessary to study its damage mechanism. In the present study, we have examined the protective effects of Ganoderma lucidum triterpenoids on oxidative stress and apoptosis in the spleen of chickens induced by Cd. One hundred and twenty healthy Hailan white chickens (7-day-old) were randomly divided into the following four groups: control group, Cd group, triterpenoid group, and Cd-triterpenoid group. The chickens were euthanized on the 20th, 40th, and 60th days, and the spleens were removed. Cd and malondialdehyde (MDA) content, antioxidant enzyme (superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)) activities, and inflammatory factor (tumor necrosis factor alpha (TNF-α) and interleukin (IL-1β and IL-6)) and apoptotic factor (caspase-3, BAX, and Bcl-2) expressions were detected. The results showed that Ganoderma lucidum triterpenoids could reduce the content of Cd and MDA; increase the antioxidant enzyme activities (SOD and GSH-Px); decrease the expression of inflammatory factors (TNF-α) and interleukin (IL-1β and IL-6); increase the expression of apoptotic factor (Bcl-2); and decrease the expression of apoptotic factors (caspase-3 and Bax). It showed that the triterpenoids of Ganoderma lucidum had significant protective effects on oxidative stress andapoptosis of chicken spleen, which provided a theoretical basis for further prevention and treatment of cadmium poisoning.

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PMID: 

Int J Immunopathol Pharmacol. 2019 Jan-Dec;33:2058738419869489. PMID: 31462112

Abstract Title: 

Antitumor activity of enzymatically hydrolyzedpolysaccharide on U14 cervical carcinoma-bearing mice.

Abstract: 

Polysaccharides fromhave been demonstrated to possess diverse biological activities. Despite lots of studies on the biological activities ofpolysaccharide (GLP), little is known regarding the medicinal potential of low-molecular weight enzymatically hydrolyzedpolysaccharide (EGLP). EGLP was prepared by enzymatic degradation and its potential effects in U14 cervical tumor-bearing mice were evaluated. Both GLP and EGLP delayed tumor growth of the tumor xenograft. The EGLP was superior to native polysaccharide. Moreover, EGLP treatment could effectively protect the immune organs of U14 cervical carcinoma-bearing mice. In addition, the EGLP treatment ameliorated oxidative stress as compared with cyclophosphamide (CTX). Compared with the MC group, the expression of Bcl-2 and COX-2 was obviously decreased by EGLP treatment, whereas the expression of Bax and cleaved caspase-3 was obviously increased. These results indicated that EGLP showed stronger antitumor activity with lower toxic effects and had the potential to be a novel antitumor agent.

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PMID: 

Integr Cancer Ther. 2019 Jan-Dec;18:1534735419880275. PMID: 31595795

Abstract Title: 

The Possible Role of PD-1 Protein in-Mediated Immunomodulation and Cancer Treatment.

Abstract: 

has been used in Chinese medicine for thousands years to improve health and to promote longevity. One important function ofis to modulate the immune system. However, the underlying mechanism is not well understood. Programmed cell death protein 1 (PD-1) is a cell surface protein present in certain immune cells (, B- and Tcells) and plays an important role in modulating the immune response. The role of PD-1 protein in-mediated immunomodulation is unknown.Cultured human Blymphocytes and extract prepared fromspores (GLE) were used to determine PD-1 protein in-mediated immunomodulation. Both western blotting and immunofluorescence (IF) microscopy assays were used to determine the effect of GLE treatment on PD-1 protein expression. A reverse transcription-based quantitative polymerase chain reaction (real-time PCR) assay was used to determine the effect of GLE on transcriptiongene.Both our western blotting and IF staining results demonstrated great reduction in PD-1 protein and in proportion of PD-1+ cells in these B-lymphocytes. Our real-time PCR results indicated that this PD-1 protein reduction was not caused by a transcriptional inhibition of the gene. In addition, our western blotting study further revealed that the GLE treatment caused an increase in expression of CCL5 chemokine in the cultured B-lymphocytes.PD-1 protein is an important target of-mediated immunomodulation.and its bioactive compounds can be developed into novel immunomodulators for prevention and treatment of cancer and many other diseases.

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PMID: 

Mutat Res. 2019 Sep ;845:403065. Epub 2019 Jun 3. PMID: 31561886

Abstract Title: 

Ganoderma Lucidum induces oxidative DNA damage and enhances the effect of 5-Fluorouracil in colorectal cancer in vitro and in vivo.

Abstract: 

The first-line chemotherapy of colorectal cancer (CRC), besides surgery, comprises administration of 5-Fluorouracil (5FU). Apart from cytotoxic effect on cancer cells, 5FU may also cause adverse side effects. Ganoderma Lucidum (GLC) is a mushroom used in Traditional Eastern Medicine. We propose that natural compounds, particularly GLC extracts, may sensitize cancer cells to conventional chemotherapeutics. This combination therapy could lead to more selective cancer cell death and may improve the response to the therapy and diminish the adverse effects of anticancer drugs. Here we demonstrate that GLC induced oxidative DNA damage selectively in colorectal cancer cell lines, whereas it protected non-malignant cells from the accumulation of reactive oxygen species. Accumulation of DNA damage caused sensitization of cancer cells to 5FU resulting in improved anticancer effect of 5FU. The results obtained in colorectal cell lines were confirmed in in vivo study: GLC co-treatment with 5FU increased the survival of treated mice and reduced the tumor volume in comparison with group treated with 5FU alone. Combination of conventional chemotherapeutics and natural compounds is a promising approach, which may reduce the effective curative dose of anticancer drugs, suppress their adverse effects and ultimately lead to better quality of life of CRC patients.

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PMID: 

J Biomol Struct Dyn. 2019 Oct 24:1-16. Epub 2019 Oct 24. PMID: 31595837

Abstract Title: 

The identification of active compounds inextract inhibiting dengue virus serine protease and its computational studies.

Abstract: 

The number of global dengue incidences is alarmingly high in recent years. The global distribution of four dengue serotypes has also added economic burden in the dengue-endemic countries. To discover the potent dengue virus inhibitors in the antler form of(Lingzhi or Reishi), the water extraction of normaland its antler form were conducted and the chemical compounds were identified by LC-MS. Six distinct chemical compounds identified in high abundance were hesperetin, thymidine, lucidenic acid, 11-aminoundecanoic acid, 5-carboxyvanillic acid and ganocin B. The water extracts ofin its antler form inhibited the DENV2 NS2B-NS3 protease activity at 84.6 ± 0.7%, higher than the normal. Then, molecular docking was performed on the homology model built from an in-house sequence. Docking simulation results showed that hesperetin and ganocin B were the best leads to bind at the catalytic triad of DENV2 NS2B-NS3pro via hydrogen bonding, van der Waals and pi-pi interactions. Extensive overlapping of HOMO-LUMO orbitals at the ringed regions of hesperetin helped to facilitate the entry of ligand to the catalytic triad cleft. LC-MS, molecular docking and density functional theory analyses confirmed that hesperetin was the strongest inhibitor against NS2B-NS3 protease. Communicated by Ramaswamy H. Sarma.

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PMID: 

J Ethnopharmacol. 2020 Jan 30 ;247:112256. Epub 2019 Oct 3. PMID: 31586690

Abstract Title: 

Ganoderma lucidum spore oil induces apoptosis of breast cancer cells in vitro and in vivo by activating caspase-3 and caspase-9.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: The mushroom Ganoderma lucidum (G. lucidum) is a traditional Chinese medicine reported to have a variety of pharmacological properties, including anti-cancer activity. G. lucidum spore oil (GLSO) is a lipid substance extracted from sporoderm-broken spore of G. lucidum. However, the effect of GLSO on breast cancer and the underlying molecular mechanism remain unclear.AIM OF THE STUDY: The aim of this study was to identify the effects of GLSO on breast cancer cells in vitro and in vivo as well as to investigate the mechanistic basis for the anticancer effect of GLSO.MATERIALS AND METHODS: First, in vitro MDA-MB-231 cells were treated with GLSO (0.2, 0.4, and 0.6 μL/mL). The protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), X-linked inhibitor of apoptosis (XIAP), total poly (ADP-ribose) polymerase (PARP), caspase-3 and caspase-8 were examined using western blotting. The mRNA expression levels of Fas-associated protein with death domain (FADD), TNF receptor-associated factor 2 (TRAF2), caspases-3, -8, -9 and Bax were examined using qRT-PCR. Second, in vivo the anticancer properties of GLSO were assessed by H&E, TUNEL and immunohistochemistry in BALB/c mice injected with 4T1 cells. In addition, the levels of caspase-9/caspase-3 signaling pathway proteins in tumor tissue were evaluated by immunoblotting. Finally, MDA-MB-231 cells were treated with caspase inhibitors to measure cell viability, the protein levels were examined with western blotting.RESULTS: The results in vitro showed that GLSO up-regulated the expression of Bax and caspase-3 in MDA-MB-231 cells, but had no effect on the expression of caspase-8. Moreover, the growth of tumors in vivo was significantly suppressed in the GLSO-treated group. The results of Western blot were consistent with in vitro. In vitro, co-treatment of MDA-MB-231 cells with caspase inhibitors reduced the inhibitory effect of GLSO on cell growth.CONCLUSIONS: GLSO inhibits the growth of MDA-MB-231 cells and tumors in vivo by inducing apoptosis, which may be achieved through the mitochondrial apoptotic pathway.

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PMID: 

Vasc Health Risk Manag. 2019 ;15:419-427. Epub 2019 Oct 3. PMID: 31632046

Abstract Title: 

Polysaccharide peptide (PsP) G: a potential inducer for vascular repair in type 2 diabetes mellitus model.

Abstract: 

Introduction: The increasing blood glucose level due to insulin resistance which occurs in diabetes mellitus (DM) may cause vascular damage. This study aims to prove the effect of the polysaccharide peptide (PsP)on improving vascular damage through an increase of circulating endothelial cells and circulating endothelial cells (CEC) ratio, decreased H2O2, triglyceride (TG), total cholesterol (TC) and insulin resistance in type 2 DM.Methods: Our study is a true experimental study with randomized posttest control group design that used 35 Wistar rats divided into five groups: normal, control (+) and three groups of different variant PsP doses 50, 150 and 300 mg/kg BW (n=7).Results: By using one-way ANOVA and post-hoc Duncan test, the results show a significant increase of endothelial progenitor cell (EPC) concentration (=0.000) and ratio EPC:CEC (0.000) by dose-dependent fashion and also reduced CEC concentration (=0.001), H2O2 (=0.03), TG (=0.001), TC (=0.01) and insulin resistance (=0.003).Conclusion: In this study, PsP induced endothelial repairing process and reduced the risk factor with 300 mg/kg BW as optimum dose. However, further research on EPC and CEC detection markers is important. Further research on PsP and clinical trial for commercial uses is also needed.

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PMID: 

Molecules. 2019 Oct 24 ;24(21). Epub 2019 Oct 24. PMID: 31653035

Abstract Title: 

Quercetin Synergistically Inhibit EBV-Associated Gastric Carcinoma withExtracts.

Abstract: 

Mycotherapy has been shown to improve the overall response rate during cancer treatment and reduce some chemotherapy-related adverse events.is a traditional mushroom used for pharmaceutical purposes.extracts (GLE) showed potential antitumor activities against several cancers. These tumor inhibitory effects of GLE were attributed to the suppression of the proliferation and metastasis of cancer cells. Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is defined as the monoclonal proliferation of carcinoma cells with latent EBV infection. The inhibitory effects of GLE against EBVaGC are questionable. The aim of this study was to investigate GLE as potential antitumor agents and a counterpart of quercetin (QCT) for the cotreatment in suppressing EBVaGC development. Therefore, this study conducted antitumor assays using a EBVaGC xenograft mice model and found that GLE could suppress tumor development. These inhibitory effects were significantly augmented by the low concentration of the quercetin (QCT) cotreatment in the xenograft mice. The addition of GLE in low concentrations synergistically reinforced QCT-induced apoptosis and EBV lytic reactivation. GLE contains various polysaccharides and triterpenes, such as ganoderic acid. Interestingly, the addition of ganoderic acid A (GAA) could produce similar bioactive effects like GLE in QCT-mediated antitumor activity. The GAA addition in low concentrations synergistically reinforced QCT-induced apoptosis and EBV lytic reactivation. GAA was sufficiently effective as much as GLE. Therefore, our results suggested that QCT-supplemented GLE could be a potential food adjunct for the prevention of EBVaGC development.

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