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Lentinula edodes (Shiitake) et cancer : Propriétés pharmacologiques, Essais cliniques et Preuves d’efficacité.

  • March 2018
  • Conference: iCEPS Conference 2018, 6ème édition. Cancer : l’efficacité des Interactions Non Médicamenteuses (Montpellier, France, 23/03/2018).
Authors:
Diallo I. at Université de Montpellier
Diallo I.
Alain Michel at Université de Montpellier
Alain Michel
Patrick Poucheret at Université de Montpellier
Patrick Poucheret
Sylvie Morel at Université de Montpellier
Sylvie Morel
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Abstract

Résumé: Diallo I., Michel A., Poucheret P., Morel S., Vitou M., Traoré L., Rapior S. et Fons F. Mots clés : Anti-tumoral, Cancer, Essais cliniques, Lentinane, Shiitake Rationnel : Le Shiitake est un champignon comestible et largement cultivé en Chine, en Europe et dans d’autres pays de l’Asie de l’Est en raison de ses propriétés nutritionnelles et pharmacologiques [1]. Les recherches effectuées ces dernières années montrent que certaines molécules de Lentinula edodes comme le lentinane possèdent une activité biologique contre le cancer [2, 3, 4, 5, 6]. Son utilisation améliore la qualité de vie et les paramètres immunitaires des patients atteints du cancer [7]. Méthodes: L’effet de Lentinula edodes associé ou non à une chimiothérapie a été testé in vitro sur des cellules HeLa [6] et sur des lignées cellulaires MDA-MD-453 de carcinome mammaire humain [12]. Des souris atteints d’un cancer ont été traitées par un polysaccharide issu du Lentinula edodes pendant plusieurs jours [10, 13]. Des études cliniques randomisées et de cohorte ont également exploré le potentiel anticancéreux du lentinane dans une méta-analyse sur 650 participants atteints d’un cancer gastrique avancé [2] et d’un extrait de Shiitake administré per os chez 20 patientes ayant un cancer de sein [7].
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1
Proposition de communication affichée
Cancer : L’efficacité des Interventions Non Médicamenteuses
Saint-Charles, Montpellier
23 mars 2018
Objectif de la communication (cocher la case correspondante)
☒ partager les preuves d’efficacité d’une INM sur la base d’une étude interventionnelle
discuter des méthodologies d’évaluation des INM
explorer un mécanisme d’action d’une INM
Thème (cocher la case correspondante)
Interventions Psychologiques Santé
Intervention Physiques Santé
Interventions Nutritionnelles Santé
Interventions Numériques Santé
☒ Autres Interventions
Méthode (cocher la case correspondante)
☒ Essai clinique randomisé contrôlé
Essai clinique contrôlé
Essai clinique sans groupe contrôle
☒ Etude de cohorte
☐ Etude de cas
Autre
Le soumis sera évalué par le comité scientifique du congrès.
La proposition doit être envoyée au plus tard le 7 février 2018.
Une réponse sera faite le 8 février 2018. En cas de demande de modification, la version corrigée devra être
renvoyée le 28 février 2018 au plus tard.
Format du poster : 0,96 m de largeur et 1,18 de hauteur
Langue : Français ou anglais
Fichier à envoyer par email à : jerome.maitre@univ-montp3.fr
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2
Titre: Lentinula edodes (Shiitake) et cancer : Propriétés Pharmacologiques, Essais Cliniques et Preuves
d’Efficacité.
Ibrahima DIALLO
1,2,3
, Alain MICHEL
2
, Patrick POUCHERET
2
, Sylvie MOREL
1
, Manon VITOU
1
,
Lonsény TRAORE
3
, Sylvie RAPIOR
1
, Françoise FONS
1
.
1. Laboratoire de Botanique, Phytochimie et Mycologie, UMR 5175 (CEFE), UFR des Sciences
Pharmaceutiques et Biologiques, Université de Montpellier, 15 avenue Charles Flahault, BP 14491,
34093 Montpellier cedex 5, France ; *ibrahima.diallo03@etu-umontpellier.fr,
sylvie.rapior@umontpellier.fr; francoise.fons@umontpellier.fr
2. Laboratoire de Pharmacologie et Physiopathologie Expérimentale, UMR 95 (Qualisud), UFR des
Sciences Pharmaceutiques et Biologiques, Université de Montpellier, 15 Avenue Charles Flahault,
34093 Montpellier cedex 5 ; patrick.poucheret@umontpellier.fr, alain.michel@umontpellier.fr
3. Laboratoire de Technologie Alimentaire du Département de Génie Chimique; Université Gamal Abdel
Nasser de Conakry. BP : 1147 Conakry-Guinée ; louncenytraore8@gmail.com
Mots clés : Anti-tumoral, Cancer, Essais cliniques, Lentinane, Shiitake
Résumé:
Rationnel : Le Shiitake est un champignon comestible et largement cultivé en Chine, en Europe et dans
d’autres pays de l’Asie de l’Est en raison de ses propriétés nutritionnelles et pharmacologiques [1]. Les
recherches effectuées ces dernières années montrent que certaines molécules de Lentinula edodes comme le
lentinane possèdent une activité biologique contre le cancer [2, 3, 4, 5, 6]. Son utilisation améliore la qualité
de vie et les paramètres immunitaires des patients atteints du cancer [7].
Méthodes: L’effet de Lentinula edodes associé ou non à une chimiothérapie a été testé in vitro sur des
cellules HeLa [6] et sur des lignées cellulaires MDA-MD-453 de carcinome mammaire humain [12]. Des
souris atteints d’un cancer ont été traitées par un polysaccharide issu du Lentinula edodes pendant plusieurs
jours [10, 13]. Des études cliniques randomisées et de cohorte ont également exploré le potentiel
anticancéreux du lentinane dans une méta-analyse sur 650 participants atteints d’un cancer gastrique avancé
[2] et d’un extrait de Shiitake administré per os chez 20 patientes ayant un cancer de sein [7].
Résultats : Les résultats in vitro suggèrent que Lentinula edodes inhibe effacement la croissance des
cellules tumorales de manière dose dépendante et favorise le processus de mort cellulaire programmée
(apoptose) [12, 6]. Des résultats semblables ont été observés in vivo (sur des souris) âgées de 7 à 8
semaines recevant une dose de 1 à 10 mg/kg du poids corporel pendant 10 jours [13]. Chez l’homme, les
études ont révélé que le lentinane possède un effet important et significatif sur la qualité de vie des patients
lorsqu’ils reçoivent oralement un extrait aqueux du mycélium du Shiitake pendant 8 semaines [7]. Il a aussi
été noté pour l’ensemble des études in vitro et in vivo, une réduction importante de la taille des tumeurs
lorsqu’on utilise les polysaccharides du Shiitake [2, 7, 10].
Discussion : Bien que les polysaccharides (lentinane) du Shiitake possèdent une action anti-tumorale sur la
plupart des cancers étudiés, il existe une controverse totale sur son mode d’action (mécanisme biologique).
Pour certains auteurs, le lentinane ne provoquerait pas une attaque directe des cellules cancéreuses, mais il
stimulerait le système immunitaire de l’hôte, en se liant à la surface des lymphocytes ou des protéines
sériques spécifiques, provoquant ainsi l’activation des macrophages et des cellules T helper [4, 8, 9]. Pour
d’autres, le lentinane exerce ses effets anti-tumoraux de façon directe contre les cellules cancéreuses ce qui
conduit à la suppression de la prolifération cellulaire et induit l’apoptose [6, 10]. Le Shiitake est un véritable
potentialisateur cellulaire permettant la production d’un grand nombre de cytokines comme IL-1, IL-2, IL-12,
TNF-α, d’interférons [8, 9, 11]. Il pourrait donc être un traitement adjuvant dans le cadre de la lutte contre le
cancer.
1. Poucheret P. et al. (2006). Biological and Pharmacological Activity of Higher Fungi: 20-Year
Retrospective Analysis. Cryptogamie, Mycologie, 27 (4) : 311-333.
https://iceps2018.fr/
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2. Oba K. et al. (2009). Individual patient based meta-analysis of lentinan for unresectable/recurrent
gastric cancer. Anticancer Research, 29 (7) : 2739-2746.
3. De Silva D. et al. (2012). Medicinal mushrooms in supportive cancer therapies: an approach to anti-
cancer effects and putative mechanisms of action. Fungal Diversity, 55 (1) : 1-35.
4. Del Buono A. et al. (2016). Polysaccharide from Lentinus edodes for integrative cancer treatment:
immunomodulatory effects on lymphocyte population. World Cancer Research Journal, 3 (1) : 1-7.
5. Singdevsachan S. et al. (2016). Mushroom polysaccharides as potential prebiotics with their antitumor
and immunomodulating properties: A review. Bioactive Carbohydrates and Dietary Fibre, 7 (1) : 1-14.
6. Ya G. (2017). A Lentinus edodes polysaccharide induces mitochondrial-mediated apoptosis in human
cervical carcinoma HeLa cells. International Journal of Biological Macromolecules, 103 (10) : 676-682.
7. Suzuki N. et al. (2013). Efficacy of Oral Administration of Lentinula edodes Mycelia Extract for Breast
Cancer Patients Undergoing Postoperative Hormone Therapy. Asian Pacific Journal of Cancer
Prevention, 14 (6) : 3469-3472.
8. Bisen P.S. et al. (2010) Lentinus edodes: A Macrofungus with Pharmalogical Activities. Current
Medicinal Chemistry, 17 (22) : 2419-2430.
9. You R.X. et al. (2014). Alkali-soluble polysaccharides isolated from Lentinus edodes, induces
apoptosis and G2/M cell cycle arrest in H22 cells through microtubule depolymerization. Phytotherapy
Research, 28 (12) : 1837-1845.
10. Wang J. et al. (2016). A polysaccharide from Lentinus edodes inhibits human colon cancer cell
proliferation and suppresses tumor growth in athymic nude mice. Oncotarget, 8 (1) : 610-623.
11. Yap A.T. et al. (2003). Immunopotentiating properties of lentinan (1- 3)-β-D-glucan extracted from
culinary-medicinal shiitake mushroom Lentinus edodes (Berk.) Singer (Agaricomycetideae).
International Journal Medicinal. Mushrooms, 5 (4) : 352-372.
12. Fang N. et al. (2006). Inhibition of Growth and Induction of Apoptosis in Human Cancer Cell Lines by
an Ethyl Acetate Fraction from Shiitake Mushrooms. The Journal of Alternative and Complementary
Medicine, 12 (2) : 125-132.
13. Zheng R. et al. (2005). Characterization and immunomodulating activities of polysaccharide from
Lentinus edodes. International Immunopharmacology, 5 (5) : 811-820.
ResearchGate has not been able to resolve any citations for this publication.
A polysaccharide from Lentinus edodes inhibits human colon cancer cell proliferation and suppresses tumor growth in athymic nude mice
Article
Full-text available
  • Nov 2016
The antitumor effect of Lentinan is thought rely on the activation of immune responses; however, little is known about whether Lentinan also directly attacks cancer cells. We therefore investigated the direct antitumor activity of SLNT (a water-extracted polysaccharide from Lentinus edodes) and its probable mechanism. We showed that SLNT significantly inhibited proliferation of HT-29 colon cancer cells and suppressed tumor growth in nude mice. Annxein V-FITC/PI, DAPI, AO/EB and H&E staining assays all showed that SLNT induced cell apoptosis both in vitro and in vivo. SLNT induced apoptosis by activating Caspase-3 via both intrinsic and extrinsic pathways, which presented as the activation of Caspases-9 and -8, upregulation of cytochrome c and the Bax/Bcl-2 ratio, downregulation of NF-κB, and overproduction of ROS and TNF-α in vitro and in vivo. Pretreatment with the caspase-3 inhibitor Ac-DEVD-CHO or antioxidant NAC blocked SLNT-induced apoptosis. These findings suggest that SLNT exerts direct antitumor effects by inducing cell apoptosis via ROS-mediated intrinsic and TNF-α-mediated extrinsic pathways. SLNT may thus represent a useful candidate for colon cancer prevention and treatment.
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Medicinal mushrooms in supportive cancer therapies: an approach to anti-cancer effects and putative mechanisms of action
Article
Full-text available
  • Jul 2012
Fungal Diversity, 55 (1), 1-35 (2012). Medicinal mushrooms have been valued as natural sources of bioactive compounds since times immemorial and have been recognized as potential immunomodulating and anti-cancer agents. Their consumption has consistently been shown to have beneficial effects on human health. Cancer is a generic term for several types of diseases that can be chronic and are responsible for a large number of deaths worldwide. Although there has been considerable progress in modern cancer therapy research, difficulties in understanding the molecular behavior of various types of cancers and the numerous side effects experienced by patients from treatments means that this whole subject area is still problematic. Thus, biological immunotherapy using natural bioactive compounds as supportive treatments in conventional cancer therapies has become in vogue. Bioactive metabolites isolated from medicinal mushrooms have shown potential successes in cancer treatment as biological immunotherapeutic agents that stimulate the immune system against cancer cells. They also act as an effective source of anti-cancer agents, capable of interfering with cellular signal transduction pathways linked to cancer development and progression. In this review we compile available data on the characteristics of medicinal mushrooms that appear to be particularly effective as biological immunotherapeutic agents. Major consideration is given to biological constituents and the putative mechanisms of action by which bioactive compounds act on the human body. Consideration is also given to the benefits that have been claimed for the use of mushrooms in treating cancer and the future prospects of using medicinal mushrooms as potent supportive candidate bioagents for treatment of cancers is discussed.
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Lentinus edodes: A Macrofungus with Pharmacological Activities
Article
Full-text available
Lentinus edodes is the first medicinal macrofungus to enter the realm of modern biotechnology. It is the second most popular edible mushroom in the global market which is attributed not only to its nutritional value but also to possible potential for therapeutic applications. Lentinus edodes is used medicinally for diseases involving depressed immune function (including AIDS), cancer, environmental allergies, fungal infection, frequent flu and colds, bronchial inflammation, heart disease, hyperlipidemia (including high blood cholesterol), hypertension, infectious disease, diabetes, hepatitis and regulating urinary inconsistencies. It is the source of several well-studied preparations with proven pharmacological properties, especially the polysaccharide lentinan, eritadenine, shiitake mushroom mycelium, and culture media extracts (LEM, LAP and KS-2). Antibiotic, anti-carcinogenic and antiviral compounds have been isolated intracellularly (fruiting body and mycelia) and extracellularly (culture media). Some of these substances were lentinan, lectins and eritadenine. The aim of this review is to discuss the therapeutic applications of this macrofungus. The potential of this macrofungus is unquestionable in the most important areas of applied biotechnology.
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A Lentinus edodes polysaccharide induces mitochondrial-mediated apoptosis in human cervical carcinoma HeLa cells
Article
  • May 2017
In this study, a homogeneous polysaccharide (LEP1) with an average molecular weight of 53kDa was successfully purified from the fruiting bodies of Lentinus edodes and its anticancer efficacy on human cervical carcinoma HeLa cells in vitro and associated possible molecular mechanism were also evaluated. MTT assay showed that LEP1 exhibited a dose-dependent inhibitory effect on the proliferation of HeLa cells and caused apoptotic death. Our present findings provided the first evidence that LEP1 induced the apoptosis of HeLa cells via a mitochondria dependent pathway, as indicated by an increase in Bax/Bcl-2 ratio, a loss of mitochondrial membrane potential (Δym), the release of cytochrome c from the mitochondria to the cytosol, activation of caspase-9 and caspase-3, and cleavage of poly (ADP-ribose) polymerase (PARP) in HeLa cells. These combined results unequivocally indicated that the involvement of mitochondria-mediated signaling pathway in LEP1-induced apoptosis and strongly provided experimental evidence for the use of LEP1 as a potential therapeutic agent in the prevention and treatment of human cervical carcinoma.
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Alkali-Soluble Polysaccharide, Isolated from Lentinus edodes, Induces Apoptosis and G2/M Cell Cycle Arrest in H-22 Cells Through Microtubule Depolymerization
Article
The aim of the study was to evaluate the pro-apoptotic effects of polysaccharides derived from Lentinus edodes and further elucidated the mechanisms of this action. Our results demonstrated that marked morphological changes of apoptosis were observed after treatment of L. edodes polysaccharides [Lentinan (LTN)]. Moreover, LTN-induced cell apoptosis was characterized by a rapid stimulation of reactive oxygen species production, the loss of mitochondrial membrane potential and an increase in intracellular concentration of Ca(2+) . In addition, the results of the haematoxylin and eosin and TUNEL assay further confirmed that LTN-induced apoptosis in vivo. Furthermore, flow cytometry analysis showed that LTN could arrest the cell cycle at G2/M phase, and immunofluorescence showed LTN caused disruption of microtubule. These results suggest that disruption of cellular microtubule network, arrest of the cell cycle at G2/M phase and induction of apoptosis may be one of the possible mechanisms of anti-tumour effect of LTN. Copyright © 2014 John Wiley & Sons, Ltd.
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Efficacy of Oral Administration of Lentinula eododes Mycelia Extract for Breast Cancer Patients Undergoing Postoperative Hormone Therapy
Article
Extract of Lentinula edodes mycelia (LEM) is currently utilized as an oral biological response modifier (BRM) medicine for cancer patients. However, its effectiveness for breast cancer patients with postoperative adjuvant hormone therapy has not yet been scientifically verified. In this study, we investigated the influence of LEM on the quality of life (QOL) and immune response in breast cancer patients undergoing postoperative adjuvant hormone therapy. Twenty patients were studied in total. They received only hormone therapy in the first 4 weeks followed by hormone therapy and LEM during the next 8 weeks. Laboratory tests, QOL score and peripheral blood cytokine production levels were evaluated during the study period. No changes in QOL or cytokines were noted after the first 4 weeks. In contrast, during the following combined therapy period, improvements were noted in QOL and cytokine levels. Although a future large-scale investigation is necessary to confirm these results, these data suggest that the concomitant use of LEM with postoperative adjuvant hormone therapy improves the QOL and immune function of patients.
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Individual Patient Based Meta-analysis of Lentinan for Unresectable/Recurrent Gastric Cancer
Article
In the present study, the effect of immunochemotherapy with lentinan compared with that of chemotherapy alone was evaluated in patients with advanced gastric cancer through individual patient data (IPD) meta-analysis. Based on a computerized and manual search, all eligible centrally randomized controlled trials (RCT) which compared chemotherapy regimens with or without lentinan administration for advanced gastric cancer patients were included. In total, 650 IPD from 5 trials were available. Lentinan significantly prolonged the overall survival (stratified log-rank p=0.011). The overall hazard ratio (HR) was 0.80 (95% confidence interval=0.68-0.95) and there was no heterogeneity between trials. Additionally, lentinan was possibly more effective in patients with lymph-node metastasis than in non-node metastasis patients (P for interaction=0.077). The addition of lentinan to standard chemotherapy offers a significant advantage over chemotherapy alone in terms of survival for patients with advanced gastric cancer.
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Characterization and immunomodulating activities of polysaccharide from Lentinus edodes
Article
The polysaccharide L-II was isolated and purified from the fruiting body of Lentinus edodes, which consisted of d-glucopyranose and had the molecular weight of 2.03 x 10(5) Da. We evaluated the effects of the polysaccharide L-II on the cellular immune response of Sarcoma 180-bearing mice. Mice were treated with three doses of the polysaccharide L-II (1, 5, and 10 mg/kg body weight) for 10 days. Tumor weight, relative spleen and thymus weight, delayed-type hypersensitivity (DTH) response, phagocytosis of macrophage, splenocytes proliferation were studied. Concentration of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) in mice serum were measured in control and polysaccharide groups. At the dose of 1, 5 and 10 mg/kg, a significant increase (p<0.05) in relative spleen and thymus weight, DTH, phagocytosis of macrophage was observed, as well as a significant decrease in tumor formation. The concentration of TNF-alpha, IFN-gamma in serum increased significantly in the polysaccharide groups compared with the model control group, but IL-2 not. Moreover, the polysaccharide L-II could increase NO production and catalase activity in macrophages. Results of these studies demonstrated the antitumor activity of the polysaccharide L-II on mice-transplanted sarcoma 180 was mediated by immunomodulation in inducing T-cells and macrophage-dependent immune system responses.
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