Polysaccharide peptides from Coriolus versicolor exert differential immunomodulatory effects on blood lymphocytes and breast cancer cell line MCF-7 in vitro

Kowalczewska, Malgorzata; Piotrowski, J; Jędrzejewski, Tomasz; Kozak, Wiesław

doi:10.1016/j.imlet.2016.04.010

Cited by 27 publications

(22 citation statements)

References 23 publications

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“…Besides, CV has been demonstrated a variety of other pharmacological effects, including anticancer, immunomodulatory, anti‐inflammatory, antioxidant activities, and memory improvements, which is beneficial for a comprehensive treatment of T2DM (Chen et al, ; Fang et al, ; Kowalczewska, Piotrowski, Jędrzejewski, & Kozak, ; Luo et al, ; Matijašević et al, ). In conclusion, we present evidence that CV extract could improve insulin resistance by increasing the translocation and expression of GLUT4 in skeletal muscle, in which both PI3K/Akt and p38 MAPK signaling pathways were involved.…”

Section: Discussionmentioning

confidence: 99%

Coriolus versicolor aqueous extract ameliorates insulin resistance with PI3K/Akt and p38 MAPK signaling pathways involved in diabetic skeletal muscle

Xian

Che

Qin

et al. 2017

Phytotherapy Research

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Patients with type 2 diabetes mellitus (T2DM) are usually with poor immunity and easier to suffer from cancer and microbial infections. Herein, we report an efficient anti-diabetic medicinal mushroom, Coriolus versicolor (CV). This study aimed to investigate the anti-diabetic and anti-insulin-resistance effects of CV aqueous extract in myoblasts (L6 cells) and skeletal muscle of T2DM rat. Our results showed that CV extract treatment significantly reduced blood glucose levels of T2DM rats, whereas CV extract increased glucose consumption in insulin resistant L6 cells. Besides, the translocation and expression of glucose transporter 4 were enhanced by CV extract, which indicated that CV extract was effective in diabetic skeletal muscle. Moreover, CV extract treatments resulted in remarkable anti-insulin-resistance effects, which was reflected by the change of gene and protein expression levels in PI3K/Akt and p38 MAPK pathways. PI3K inhibitor, LY29004, and p38 MAPK inhibitor, SB203580 confirmed it further. In conclusion, our results demonstrated that the CV extract exhibited anti-diabetic and anti-insulin-resistance effects in diabetic skeletal muscle, and the effects were mediated by PI3K/Akt and p38 MAPK pathways. These findings are remarkable when considering the use of commercially available CV by diabetic patients who also suffer from cancer or microbial infections.

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Section: Discussionmentioning

confidence: 99%

Coriolus versicolor aqueous extract ameliorates insulin resistance with PI3K/Akt and p38 MAPK signaling pathways involved in diabetic skeletal muscle

Xian

Che

Qin

et al. 2017

Phytotherapy Research

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“…Previously, we have shown that CV‐derived polysaccharide peptides, induce differential effects depending on target cells (Kowalczewska, Piotrowski, Jędrzejewski, & Kozak, ). Acting as biological response modifiers, PBPs exert strong immune‐enhancing effect on blood lymphocytes and show strong tumor inhibitory properties.…”

Section: Introductionmentioning

confidence: 99%

Coriolus versicolor‐derived protein‐bound polysaccharides trigger the caspase‐independent cell death pathway in amelanotic but not melanotic melanoma cells

Pawlikowska

Piotrowski

Jędrzejewski

et al. 2019

Phytotherapy Research

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We have investigated the potential cell death mechanism promoted by Coriolus versicolor fungus‐derived protein‐bound polysaccharides (PBPs) in melanoma cells. Knowing that melanogenesis has the potential to affect the tumor behavior and melanoma therapy outcome, the cytotoxic effects of PBPs were evaluated in human SKMel‐188 melanoma cell line, whose phenotype, amelanotic versus pigmented, depends on the concentration of melanin precursors in the culture medium. Our results showed that inhibitory effect of PBPs (100 and 200 μg/ml) towards melanoma cells is inversely associated with the pigmentation level. This cytotoxicity induced in nonpigmented melanoma cells by PBPs was caspase‐independent; however, it was accompanied by an increased intracellular reactive oxygen species (ROS) generation. The ROS production was controlled by c‐Jun N‐terminal kinase (JNK) because SP600125, a JNK inhibitor, significantly reduced ROS generation and protected cells against PBPs‐induced death. We also found that PBPs‐induced lactate dehydrogenase release in amelanotic melanoma cells was abolished by co‐treatment with receptor‐interacting serine/threonine‐protein kinase 1 inhibitor, implying engagement of this kinase in PBPs‐induced death pathway. The results suggest that PBPs induce an alternative programmed cell death, regulated by receptor‐interacting protein‐1 and ROS and that this process is modified by melanin content in melanoma cells. These findings are remarkable when considering the use of commercially available Coriolus versicolor by patients who suffer from melanoma cancer.

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“…IL-6 is a pleiotropic cytokine and an essential biomarker in the cytokine cascade that is involved in the initiation and regulation of inflammation ( 43 , 44 ). It can be synthesized by dendritic cells, macrophages ( 45 , 46 ), lymphocytes ( 47 – 50 ), somatic cells (e.g., fibroblasts, keratinocytes, endothelial cells) ( 51 – 53 ), and multiple cancer cell types including breast, lung, head and neck, colorectal, hepatobiliary, pancreatic, as well as ovarian cancer cells ( 54 – 62 ).…”

Section: Introductionmentioning

confidence: 99%

Interleukin 6 Present in Inflammatory Ascites from Advanced Epithelial Ovarian Cancer Patients Promotes Tumor Necrosis Factor Receptor 2-Expressing Regulatory T Cells

et al. 2017

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BackgroundEpithelial ovarian cancer (EOC) remains a highly lethal gynecological malignancy. Ascites, an accumulation of peritoneal fluid present in one-third of patients at presentation, is linked to poor prognosis. High levels of regulatory T cells (Tregs) in ascites are correlated with tumor progression and reduced survival. Malignant ascites harbors high levels of Tregs expressing the tumor necrosis factor receptor 2 (TNFR2), as well as pro-inflammatory factors such as interleukin 6 (IL-6) and tumor necrosis factor (TNF). IL-6 is also associated with poor prognosis. Herein, we study the effect of IL-6 and TNF present in ascites on the modulation of TNFR2 expression on T cells, and specifically Tregs.MethodsAscites and respective peripheral blood sera were collected from 18 patients with advanced EOC and soluble biomarkers, including IL-6, sTNFR2, IL-10, TGF-β, and TNF, were quantified using multiplexed bead-based immunoassay. Peripheral blood mononuclear cells (PBMC) from healthy donors were incubated with cell-free ascites for 48 h (or media as a negative control). In some experiments, IL-6 or TNF within the ascites were neutralized by using monoclonal antibodies. The phenotype of TNFR2+ Tregs and TNFR2− Tregs were characterized post incubation in ascites. In some experiments, cell sorted Tregs were utilized instead of PBMC.ResultsHigh levels of immunosuppressive (sTNFR2, IL-10, and TGF-β) and pro-inflammatory cytokines (IL-6 and TNF) were present in malignant ascites. TNFR2 expression on all T cell subsets was higher in post culture in ascites and highest on CD4+CD25hiFoxP3+ Tregs, resulting in an increased TNFR2+ Treg/effector T cell ratio. Furthermore, TNFR2+ Tregs conditioned in ascites expressed higher levels of the functional immunosuppressive molecules programmed cell death ligand-1, CTLA-4, and GARP. Functionally, TNFR2+ Treg frequency was inversely correlated with interferon-gamma (IFN-γ) production by effector T cells, and was uniquely able to suppress TNFR2+ T effectors. Blockade of IL-6, but not TNF, within ascites decreased TNFR2+ Treg frequency. Results indicating malignant ascites promotes TNFR2 expression, and increased suppressive Treg activity using PBMC were confirmed using purified Treg subsets.ConclusionIL-6 present in malignant ovarian cancer ascites promotes increased TNFR2 expression and frequency of highly suppressive Tregs.

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Polysaccharide peptides from Coriolus versicolor exert differential immunomodulatory effects on blood lymphocytes and breast cancer cell line MCF-7 in vitro

Cited by 27 publications

References 23 publications

Coriolus versicolor aqueous extract ameliorates insulin resistance with PI3K/Akt and p38 MAPK signaling pathways involved in diabetic skeletal muscle

Coriolus versicolor aqueous extract ameliorates insulin resistance with PI3K/Akt and p38 MAPK signaling pathways involved in diabetic skeletal muscle

Coriolus versicolor‐derived protein‐bound polysaccharides trigger the caspase‐independent cell death pathway in amelanotic but not melanotic melanoma cells

Interleukin 6 Present in Inflammatory Ascites from Advanced Epithelial Ovarian Cancer Patients Promotes Tumor Necrosis Factor Receptor 2-Expressing Regulatory T Cells

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