Therapeutic effects of lentinan on inflammatory bowel disease and colitis‐associated cancer

Liu, Yanrong; Zhao, Jianmin; Zhao, Yali; Zong, Shumin; Tian, Yixuan; Chen, Shuang; Li, Meng; Liu, Huijuan; Zhang, Qiang; Jing, Xue-shuang; Sun, Bo; Wang, Hongzhi; Sun, Tao; Yang, Cheng

doi:10.1111/jcmm.13897

Cited by 68 publications

(42 citation statements)

References 59 publications

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“… 18 , 19 Furthermore, other reports have indicated that LNT can shift the cytokine activities of T helper (Th) cells toward Th1 cells by altering the equilibrium between reductive and oxidative macrophages. 20 Therefore, it is reasonable to propose that in this bladder cancer model, LNT initially induced macrophage activation, then enhanced the proliferation of CD4 + and CD8 + T cells, and finally upregulated the expression of IFN-γ and IL-2. 21 , 22 Meanwhile, the percentages of MDSCs and Tregs were downregulated, leading to a reduction of the anti-inflammatory cytokines IL-10 and TGF-β.…”

Section: Discussionmentioning

confidence: 87%

Lentinan Inhibits Tumor Progression by Immunomodulation in a Mouse Model of Bladder Cancer

Sun

Zhang

et al. 2020

Integr Cancer Ther

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Background: Lentinan (LNT), an isolated traditional Chinese herbal component, has antitumor potential. In the current study, the intrinsic mechanism of LNT-induced immunity against bladder cancer was explored in a mouse model. Methods: In the mouse model of bladder cancer, we used flow cytometry to detect the LNT caused population changes of T cells, macrophages, MDSC cells, and Treg cells. ELISA was used to evaluate cytokines expression in the supernatant of splenocytes. Results: We found that the administration of LNT increased the proportions of CD3+CD4+ and CD3+CD8+ T cell subsets as well as CD11b+F480+ macrophages, whereas it diminished the subpopulations of CD4+CD25+Foxp3+ regulatory T cells (Tregs) and Gr-1+CD11b+ myeloid-derived suppressor cells (MDSCs). LNT also upregulated the expression of interferon (IFN)-γ and interleukin (IL)-12, accompanied by a significant reduction in IL-10 and tumor growth factor (TGF)-β ( P < .05). Our research further confirmed the synergy between LNT and gemcitabine (GEM) to activate immunity and inhibit the growth of bladder tumors in mouse model. Conclusions: LNT induced macrophage activation, followed by the enhanced proliferation of CD4+ and CD8+ T cells, and the upregulated expression of IFN-γ and IL-2. Meanwhile, the proportions of MDSCs and Tregs were downregulated, leading to a reduced expression of the anti-inflammatory cytokines IL-10 and TGF-β. The synergy between LNT and GEM provides additional evidence supporting the application of this traditional Chinese herbal component for bladder cancer therapy.

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Section: Discussionmentioning

confidence: 87%

Lentinan Inhibits Tumor Progression by Immunomodulation in a Mouse Model of Bladder Cancer

Sun

Zhang

et al. 2020

Integr Cancer Ther

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“…Although a large number of studies have proposed treatments for this disease, a safe and therapeutic strategy is still urgently needed. Lentinan, a polysaccharide derived from Lentinus edodes, has shown protective properties in inflammatory skin diseases, 26 inflammatory bowel disease, 27 and different cancers. 28 In the present study, we employed lentinan to antagonize inflammation induced by AGEs in human chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Lentinan was purchased from Kaifeng Pharmaceutical Co. (Henan, China) 22 as powder in a penicillin bottle. Lentinan was dissolved in PBS right before use.…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

“…17 Previous research has demonstrated that lentinan exerts important antiviral, anti-cancer, and anti-inflammatory effects. [18][19][20][21] As a biological response modifier (BRM), lentinan actualizes its effects by restoring and enhancing immune system responsiveness to stimulation and other physiologically active factors. These functions indicate that lentinan may have a protective effect on chondrocytes in OA.…”

Section: Introductionmentioning

confidence: 99%

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<p>Lentinan Inhibits AGE-Induced Inflammation and the Expression of Matrix-Degrading Enzymes in Human Chondrocytes</p>

Zhang¹,

Zha²,

Zhao³

et al. 2020

DDDT

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Background: Chondrocyte-mediated inflammation is an important pathological component of osteoarthritis (OA) development. There are currently no therapies that completely reverse the development of OA. Lentinan, a type of polysaccharide derived from Lentinus edodes, has been demonstrated to possess significant anti-viral, anti-cancer, and anti-inflammatory effects, and has been recently used in the treatment of several inflammatory diseases. However, little research has focused on the pharmacological effect of lentinan in human OA. Materials and Methods: We evaluated the anti-inflammatory and anti-ROS effects of lentinan in SW1353 chondrocytes treated with AGEs using real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and the nitro oxide-specific stain DAF-FM DA. The regulatory effects of lentinan on NF-κB and MAPK p38 signaling were investigated via promoter assay and Western blot analysis. Results: We found that lentinan inhibits the production of pro-inflammatory cytokines, including IL-1β, TNF-α, IL-8 and the secretion of PGE 2 and NO, by reducing the expression of COX-2 and iNOS in AGE-challenged chondrocytes. Lentinan also reduces AGE-induced increased expression of matrix metalloproteinases-1, −3, and −13 (MMP-1, MMP-3, MMP-13). Furthermore, lentinan has a similar effect on a disintegrin and metalloproteinase with thrombospondin motifs-4 and −5 (ADAMTS-4, ADAMTS-5). Mechanistically, lentinan reduces the activation of NF-κB. Conclusion: Our findings indicate that lentinan shows a protective effect against AGEinduced inflammatory response in chondrocytes. These findings suggest that lentinan is a promising agent for the treatment of OA that could be used as a dietary supplement for patients with OA.

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“…Lentinan (LNT) is a special type of β-glucan obtained from Lentinus edode and has a wide variety of biological and physiological activities 13 . LNT is used in clinics for the treatment of malignant ascites in China, which has high security but low efficiency 14 , 15 . Selenium (Se) has a potential application in cancer therapy due to its excellent biological activity and low toxicity 16 , 17 .…”

Section: Introductionmentioning

confidence: 99%

Lentinan-functionalized Selenium Nanoparticles target Tumor Cell Mitochondria via TLR4/TRAF3/MFN1 pathway

et al. 2020

Self Cite

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Rationale: Malignant ascites caused by cancer cells results in poor prognosis and short average survival time. No effective treatment is currently available for malignant ascites. In this study, the effects of lentinan (LNT)-functionalized selenium nanoparticles (Selene) on malignant ascites were evaluated. Furthermore, the mechanism of Selene targeting mitochondria of tumor cells were also investigated. Methods: Selene were synthesized and characterized by TEM, AFM and particle size analysis. The OVCAR-3 and EAC cells induced ascites models were used to evaluate the effects of Selene on malignant ascites. Proteomic analysis, immunofluorescence, TEM and ICP-MS were used to determine the location of Selene in tumor cells. Mitochondrial membrane potential, ROS, ATP content, and caspase-1/3 activity were detected to evaluate the effect of Selene on mitochondrial function and cell apoptosis. Immunofluorescence, Co-IP, pull-down, duolink, Western blot, and FPLC were used to investigate the pathway of Selene targeting mitochondria. Results: Selene could effectively inhibit ascites induced by OVCAR-3 and EAC cells. Selene was mainly located in the mitochondria of tumor cells and induced apoptosis of tumor cells. The LNT in Selene was involved in caveolae-mediated endocytosis through the interaction between toll-like receptor-4 (TLR4) and caveolin 1 (CAV1). Furthermore, the Selene in the endocytic vesicles could enter the mitochondria via the mitochondrial membrane fusion pathway, which was mediated by TLR4/TNF receptor associated factor 3 (TRAF3)/mitofusin-1 (MFN1) protein complex. Conclusion: Selene is a candidate anticancer drug for the treatment of malignant ascites. And TLR4/TRAF3/MFN1 may be a specific nano-drug delivery pathway that could target the mitochondria.

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Therapeutic effects of lentinan on inflammatory bowel disease and colitis‐associated cancer

Cited by 68 publications

References 59 publications

Lentinan Inhibits Tumor Progression by Immunomodulation in a Mouse Model of Bladder Cancer

Lentinan Inhibits Tumor Progression by Immunomodulation in a Mouse Model of Bladder Cancer

<p>Lentinan Inhibits AGE-Induced Inflammation and the Expression of Matrix-Degrading Enzymes in Human Chondrocytes</p>

Lentinan-functionalized Selenium Nanoparticles target Tumor Cell Mitochondria via TLR4/TRAF3/MFN1 pathway

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