Mushroom β-glucans as anticancer and therapeutic agents: a focus on their mechanism of action

Authors

  • Veronika Fialková Research Centre AgroBioTech, Slovak University of Agriculture in Nitra
  • Hana Ďúranová Research centre AgroBioTech, Slovak University of Agriculture in Nitra
  • Miroslava Požgajová Research centre AgroBioTech, Slovak University of Agriculture in Nitra
  • Zuzana Chlebová Research centre AgroBioTech, Slovak University of Agriculture in Nitra

Keywords:

mushrooms, β-Glucans, anticancer effects, therapeutic potential

Abstract

β-glucans are biologically active polysaccharides derived from natural sources, especially mushrooms, renowned for their immunomodulatory, antitumor, and anti-inflammatory properties. These compounds can be safely consumed as dietary supplements or as part of one's daily diet. Chemoprevention is a crucial approach in reducing cancer development and tumor progression including the use of natural substances to impede, arrest, or reverse carcinogenesis. β-glucans, especially those from mushrooms, have been recognized as effective chemopreventive and adjuvant agents when combined with standard chemotherapy. They appear to operate through various mechanisms and may exhibit additive or synergistic effects. While in vitro and animal studies have consistently demonstrated their medical potential, clinical investigations into the precise mechanisms of action remain limited. Therefore, understanding the specific molecular changes that drive cancer development and progression, and developing anticancer and adjuvant chemotherapeutic drugs, which improve cancer treatment is still a main challenge in this field. Therefore, this review aims to summarise recent research findings on the anticancer effects of selected mushroom β-glucans, covering a range of preclinical (in vitro and in vivo) and several clinical studies, with a focus on their chemopreventive and chemotherapeutic potential. We also discuss their potential molecular mechanisms of action and provide a brief overview of the classification, structural characteristics, sources, and origin of β-glucans derived from various edible mushrooms.

References

Afiati, F., Firza, S. F., Kusmiati, & Aliya, L. S. (2019). The effectiveness β-glucan of shiitake mushrooms and Saccharomyces cerevisiae as antidiabetic and antioxidant in mice Sprague Dawley induced alloxan. AIP Conference Proceedings, 2120(1), 070006. https://doi.org/10.1063/1.5115723

Aimanianda, V., Clavaud, C., Simenel, C., Fontaine, T., Delepierre, M., & Latgé, J.-P. (2009). Cell Wall β-(1,6)-Glucan of Saccharomyces cerevisiae: STRUCTURAL CHARACTERIZATION AND IN SITU SYNTHESIS*. Journal of Biological Chemistry, 284(20), 13401–13412. https://doi.org/10.1074/jbc.M807667200

Alonso, E. N., Ferronato, M. J., Fermento, M. E., Gandini, N. A., Romero, A. L., Guevara, J. A., Facchinetti, M. M., & Curino, A. C. (2018). Antitumoral and antimetastatic activity of Maitake D-Fraction in triple-negative breast cancer cells. Oncotarget, 9(34), 23396–23412. https://doi.org/10.18632/oncotarget.25174

Ayeka, P. A. (2018). Potential of Mushroom Compounds as Immunomodulators in Cancer Immunotherapy: A Review. Evidence-Based Complementary and Alternative Medicine : eCAM, 2018, 7271509. https://doi.org/10.1155/2018/7271509

Barsanti, L., Vismara, R., Passarelli, V., & Gualtieri, P. (2001). Paramylon (β-1,3-glucan) content in wild type and WZSL mutant of Euglena gracilis. Effects of growth conditions. Journal of Applied Phycology, 13(1), 59–65. https://doi.org/10.1023/A:1008105416065

Berovic, M., Habijanic, J., Zore, I., Wraber, B., Hodzar, D., Boh, B., & Pohleven, F. (2003). Submerged cultivation of Ganoderma lucidum biomass and immunostimulatory effects of fungal polysaccharides. Journal of Biotechnology, 103(1), 77–86. https://doi.org/10.1016/s0168-1656(03)00069-5

Bobadilla, F., Rodriguez-Tirado, C., Imarai, M., Galotto, M. J., & Andersson, R. (2013). Soluble β-1,3/1,6-glucan in seaweed from the southern hemisphere and its immunomodulatory effect. Carbohydrate Polymers, 92(1), 241–248. https://doi.org/10.1016/j.carbpol.2012.09.071

Chaichian, S., Moazzami, B., Sadoughi, F., Haddad Kashani, H., Zaroudi, M., & Asemi, Z. (2020). Functional activities of beta-glucans in the prevention or treatment of cervical cancer. Journal of Ovarian Research, 13. https://doi.org/10.1186/s13048-020-00626-7

Chen, S.-N., Chang, C.-S., Hung, M.-H., Chen, S., Wang, W., Tai, C.-J., & Lu, C.-L. (2014). The Effect of Mushroom Beta-Glucans from Solid Culture of Ganoderma lucidum on Inhibition of the Primary Tumor Metastasis. Evidence-Based Complementary and Alternative Medicine, 2014, e252171. https://doi.org/10.1155/2014/252171

Chihara, G., Hamuro, J., Maeda, Y. Y., Arai, Y., & Fukuoka, F. (1970). Fractionation and Purification of the Polysaccharides with Marked Antitumor Activity, Especially Lentinan, from Lentinus edodes (Berk.) Sing. (An Edible Mushroom)1. Cancer Research, 30(11), 2776–2781.

del Fresno, C., Soulat, D., Roth, S., Blazek, K., Udalova, I., Sancho, D., & Ardavín, C. (2013). Interferon-β production via Dectin-1-Syk-IRF5 signaling in dendritic cells is crucial for immunity to C. albicans. Immunity, 38(6), 1176-1186.

Deng, G., Lin, H., Seidman, A., Fornier, M., D’Andrea, G., Wesa, K., Yeung, S., Cunningham-Rundles, S., Vickers, A. J., & Cassileth, B. (2009). A phase I/II trial of a polysaccharide extract from Grifola frondosa (Maitake mushroom) in breast cancer patients: Immunological effects. Journal of Cancer Research and Clinical Oncology, 135(9), 1215–1221. https://doi.org/10.1007/s00432-009-0562-z

Duan, T., Du, Y., Xing, C., Wang, H. Y., & Wang, R. F. (2022). Toll-like receptor signaling and its role in cell-mediated immunity. Frontiers in Immunology, 13, 812774.

Filiz, A. K., Joha, Z., & Yulak, F. (2021). Mechanism of anti-cancer effect of β-glucan on SH-SY5Y cell line. ||| Bangladesh Journal of Pharmacology |||, 16(4), Article 4.

George, B. P., Chandran, R., & Abrahamse, H. (2021). Role of Phytochemicals in Cancer Chemoprevention: Insights. Antioxidants, 10(9), 1455. https://doi.org/10.3390/antiox10091455

Golian, M., Chlebová, Z., Žiarovská, J., Benzová, L., Urbanová, L., Hovaňáková, L., Chlebo, P., & Urminská, D. (2022). Analysis of Biochemical and Genetic Variability of Pleurotus ostreatus Based on the β-Glucans and CDDP Markers. Journal of Fungi, 8(6), Article 6. https://doi.org/10.3390/jof8060563

Herrera, M. P., Gao, J., Vasanthan, T., Temelli, F., & Henderson, K. (2016). β-Glucan content, viscosity, and solubility of Canadian grown oat as influenced by cultivar and growing location. Canadian Journal of Plant Science, 96(2), 183–196. https://doi.org/10.1139/cjps-2014-0440

Hong, F., Hansen, R. D., Yan, J., Allendorf, D. J., Baran, J. T., Ostroff, G. R., & Ross, G. D. (2003). Beta-glucan functions as an adjuvant for monoclonal antibody immunotherapy by recruiting tumoricidal granulocytes as killer cells. Cancer Research, 63(24), 9023–9031.

Ina, K., Furuta, R., Kataoka, T., Kayukawa, S., Yoshida, T., Miwa, T., Yamamura, Y., & Takeuchi, Y. (2011). Lentinan prolonged survival in patients with gastric cancer receiving S-1-based chemotherapy. World Journal of Clinical Oncology, 2(10), 339–343. https://doi.org/10.5306/wjco.v2.i10.339

Izydorczyk, M. S., & Dexter, J. E. (2008). Barley β-glucans and arabinoxylans: Molecular structure, physicochemical properties, and uses in food products–a Review. Food Research International, 41(9), 850–868. https://doi.org/10.1016/j.foodres.2008.04.001

JEDINAK, A., & SLIVA, D. (2008). Pleurotus ostreatus inhibits proliferation of human breast and colon cancer cells through p53-dependent as well as p53-independent pathway. International Journal of Oncology, 33(6), 1307–1313.

Jesenak, M., Majtan, J., Rennerova, Z., Kyselovic, J., Banovcin, P., & Hrubisko, M. (2013). Immunomodulatory effect of pleuran (β-glucan from Pleurotus ostreatus) in children with recurrent respiratory tract infections. International Immunopharmacology, 15(2), 395–399. https://doi.org/10.1016/j.intimp.2012.11.020

Kaur, R., Sharma, M., Ji, D., Xu, M., & Agyei, D. (2020). Structural Features, Modification, and Functionalities of Beta-Glucan. Fibers, 8(1), Article 1. https://doi.org/10.3390/fib8010001

Kimberg, M., & Brown, G. D. (2008). Dectin-1 and its role in antifungal immunity. Medical mycology, 46(7), 631-636. https://doi.org/10.1080/13693780802140907

Kobayashi, H., Yoshida, R., Kanada, Y., Fukuda, Y., Yagyu, T., Inagaki, K., Kondo, T., Kurita, N., Suzuki, M., Kanayama, N., & Terao, T. (2005). Suppressing effects of daily oral supplementation of beta-glucan extracted from Agaricus blazei Murill on spontaneous and peritoneal disseminated metastasis in mouse model. Journal of Cancer Research and Clinical Oncology, 131(8), 527–538. https://doi.org/10.1007/s00432-005-0672-1

Kodama, N., Komuta, K., & Nanba, H. (2002). Can maitake MD-fraction aid cancer patients? Alternative Medicine Review: A Journal of Clinical Therapeutic, 7(3), 236–239.

Landis-Piwowar, K. R., & Iyer, N. R. (2014). Cancer Chemoprevention: Current State of the Art. Cancer Growth and Metastasis, 7, 19. https://doi.org/10.4137/CGM.S11288

Lavi, I., Friesem, D., Geresh, S., Hadar, Y., & Schwartz, B. (2006). An aqueous polysaccharide extract from the edible mushroom Pleurotus ostreatus induces anti-proliferative and pro-apoptotic effects on HT-29 colon cancer cells. Cancer Letters, 244(1), 61–70. https://doi.org/10.1016/j.canlet.2005.12.007

Lazaridou, A., Biliaderis, C., & Izydorczyk, M. (2007). Cereal Β-glucans: Structures, Physical Properties and Physiological Functions. In Functional Food Carbohydrates (pp. 1–72).

Lee, Y.-T., & Kim, Y.-S. (2005). Water—Solubility of β—Glucans in Various Edible Mushrooms. Journal of Food Science and Nutrition, 10(3), 294–297.

Leong, Y. K., Yang, F.-C., & Chang, J.-S. (2021). Extraction of polysaccharides from edible mushrooms: Emerging technologies and recent advances. Carbohydrate Polymers, 251, 117006. https://doi.org/10.1016/j.carbpol.2020.117006

Leung, M. Y. K., Fung, K. P., & Choy, Y. M. (1997). The isolation and characterization of an immunomodulatory and anti-tumor polysaccharide preparation from Flammulina velutipes. Immunopharmacology, 35(3), 255–263. https://doi.org/10.1016/S0162-3109(96)00157-9

Li, X., Luo, H., Ye, Y., Chen, X., Zou, Y., Duan, J., & Xiang, D. (2019). Β‑glucan, a dectin‑1 ligand, promotes macrophage M1 polarization via NF‑κB/autophagy pathway. International Journal of Oncology, 54(1), 271–282. https://doi.org/10.3892/ijo.2018.4630

Liu, X., Lv, K., Wang, J., Lin, C., Liu, H., Zhang, H., & Xu, J. (2023). C-type lectin receptor Dectin-1 blockade on tumour-associated macrophages improves anti-PD-1 efficacy in gastric cancer. British Journal of Cancer, 129(4), 721-732.

Mirończuk-Chodakowska, I., Kujawowicz, K., & Witkowska, A. M. (2021). Beta-Glucans from Fungi: Biological and Health-Promoting Potential in the COVID-19 Pandemic Era. Nutrients, 13(11), Article 11. https://doi.org/10.3390/nu13113960

Mohammadi, A., Shojaosadati, S. A., Tehrani, H. J., Mousavi, S. M., Saleh, T., & Khorasani, A. C. (2018). Schizophyllan production by newly isolated fungus Schizophyllum commune IBRC-M 30213: Optimization of culture medium using response surface methodology. Annals of Microbiology, 68(1), Article 1. https://doi.org/10.1007/s13213-017-1316-9

Morales, D., Smiderle, F. R., Villalva, M., Abreu, H., Rico, C., Santoyo, S., Iacomini, M., & Soler-Rivas, C. (2019). Testing the effect of combining innovative extraction technologies on the biological activities of obtained β-glucan-enriched fractions from Lentinula edodes. Journal of Functional Foods, 60, 103446. https://doi.org/10.1016/j.jff.2019.103446

Mudgil, D. (2017). Chapter 3—The Interaction Between Insoluble and Soluble Fiber. In R. A. Samaan (Ed.), Dietary Fiber for the Prevention of Cardiovascular Disease (pp. 35–59). Academic Press. https://doi.org/10.1016/B978-0-12-805130-6.00003-3

Murphy, E. J., Rezoagli, E., Pogue, R., Simonassi-Paiva, B., Abidin, I. I. Z., Fehrenbach, G. W., O’Neil, E., Major, I., Laffey, J. G., & Rowan, N. (2022). Immunomodulatory activity of β-glucan polysaccharides isolated from different species of mushroom—A potential treatment for inflammatory lung conditions. The Science of the Total Environment, 809, 152177. https://doi.org/10.1016/j.scitotenv.2021.152177

Noda, K., Takeuchi, S., Yajima, A., Akiya, K., Kasamatsu, T., Tomoda, Y., Ozawa, M., Sekiba, K., Sugimori, H., & Hashimoto, S. (1992). Clinical effect of sizofiran combined with irradiation in cervical cancer patients: A randomized controlled study. Cooperative Study Group on SPG for Gynecological Cancer. Japanese Journal of Clinical Oncology, 22(1), 17–25.

Piska, K., Sułkowska-Ziaja, K., & Muszyńska, B. (2017). EDIBLE MUSHROOM Pleurotus ostreatus (OYSTER MUSHROOM) – ITS DIETARY SIGNIFICANCE AND BIOLOGICAL ACTIVITY. Acta Scientiarum Polonorum Hortorum Cultus, 16(1), Article 1.

Rakszegi, M., Lovegrove, A., Balla, K., Láng, L., Bedő, Z., Veisz, O., & Shewry, P. R. (2014). Effect of heat and drought stress on the structure and composition of arabinoxylan and β-glucan in wheat grain. Carbohydrate Polymers, 102, 557–565. https://doi.org/10.1016/j.carbpol.2013.12.005

Seifert, L., Deutsch, M., Alothman, S., Alqunaibit, D., Werba, G., Pansari, M., ... & Miller, G. (2015). Dectin-1 regulates hepatic fibrosis and hepatocarcinogenesis by suppressing TLR4 signaling pathways. Cell reports, 13(9), 1909-1921.

Schwartz, B., & Hadar, Y. (2014). Possible mechanisms of action of mushroom-derived glucans on inflammatory bowel disease and associated cancer. Annals of Translational Medicine, 2(2), Article 2. https://doi.org/10.3978/j.issn.2305-5839.2014.01.03

Sima, P., Richter, J., & Vetvicka, V. (2019). Glucans as New Anticancer Agents. Anticancer Research, 39(7), 3373–3378. https://doi.org/10.21873/anticanres.13480

Sorimachi, K., Akimoto, K., Ikehara, Y., Inafuku, K., Okubo, A., & Yamazaki, S. (2001). Secretion of TNF-α, IL-8 and Nitric Oxide by Macrophages Activated with Agaricus blazei Murill Fractions in Vitro. Cell Structure and Function, 26(2), 103–108. https://doi.org/10.1247/csf.26.103

Spacek, J., Vocka, M., Zavadova, E., Konopasek, B., & Petruzelka, L. (2022). Immunomodulation with β-glucan from Pleurotus ostreatus in patients with endocrine-dependent breast cancer. Immunotherapy, 14(1), 31–40. https://doi.org/10.2217/imt-2021-0069

Sporn, M. B., & Suh, N. (2002). Chemoprevention: An essential approach to controlling cancer. Nature Reviews Cancer, 2(7), 537–543. https://doi.org/10.1038/nrc844

Steimbach, L., Borgmann, A. V., Gomar, G. G., Hoffmann, L. V., Rutckeviski, R., de Andrade, D. P., & Smiderle, F. R. (2021). Fungal beta-glucans as adjuvants for treating cancer patients – A systematic review of clinical trials. Clinical Nutrition, 40(5), 3104–3113. https://doi.org/10.1016/j.clnu.2020.11.029

Sun, M., Zhao, W., Xie, Q., Zhan, Y., & Wu, B. (2015). Lentinan reduces tumor progression by enhancing gemcitabine chemotherapy in urothelial bladder cancer. Surgical Oncology, 24(1), 28–34. https://doi.org/10.1016/j.suronc.2014.11.002

Therkelsen, S. P., Hetland, G., Lyberg, T., Lygren, I., & Johnson, E. (2016). Cytokine Levels After Consumption of a Medicinal Agaricus blazei Murill-Based Mushroom Extract, AndoSanTM, in Patients with Crohn’s Disease and Ulcerative Colitis in a Randomized Single-Blinded Placebo-Controlled Study. Scandinavian Journal of Immunology, 84(6), 323–331. https://doi.org/10.1111/sji.12476

Tripodi, F., Falletta, E., Leri, M., Angeloni, C., Beghelli, D., Giusti, L., Milanesi, R., Sampaio-Marques, B., Ludovico, P., Goppa, L., Rossi, P., Savino, E., Bucciantini, M., & Coccetti, P. (2022). Anti-Aging and Neuroprotective Properties of Grifola frondosa and Hericium erinaceus Extracts. Nutrients, 14(20), Article 20. https://doi.org/10.3390/nu14204368

Vetter, J. (2019). Biological values of cultivated mushrooms—A review. Acta Alimentaria, 48(2), 229–240. https://doi.org/10.1556/066.2019.48.2.11

Vetter, J. (2023). The Mushroom Glucans: Molecules of High Biological and Medicinal Importance. Foods, 12(5), Article 5. https://doi.org/10.3390/foods12051009

Vetvicka, V., Teplyakova, T. V., Shintyapina, A. B., & Korolenko, T. A. (2021). Effects of Medicinal Fungi-Derived β-Glucan on Tumor Progression. Journal of Fungi, 7(4), 250. https://doi.org/10.3390/jof7040250

Wang, J.-L., Bi, Z., Zou, J.-W., & Gu, X.-M. (2012). Combination therapy with lentinan improves outcomes in patients with esophageal carcinoma. Molecular Medicine Reports, 5(3), 745–748. https://doi.org/10.3892/mmr.2011.718

Wang, W.-J., Wu, Y.-S., Chen, S., Liu, C.-F., & Chen, S.-N. (2015). Mushroom β-Glucan May Immunomodulate the Tumor-Associated Macrophages in the Lewis Lung Carcinoma. BioMed Research International, 2015, 604385. https://doi.org/10.1155/2015/604385

Wasser, S. P. (2014). Medicinal mushroom science: Current perspectives, advances, evidences, and challenges. Biomedical Journal, 37(6), 345–356. https://doi.org/10.4103/2319-4170.138318

Zhang, M., Zhang, Y., Zhang, L., & Tian, Q. (2019). Mushroom polysaccharide lentinan for treating different types of cancers: A review of 12 years clinical studies in China. In Progress in Molecular Biology and Translational Science (Vol. 163, pp. 297–328). Elsevier. https://doi.org/10.1016/bs.pmbts.2019.02.013

Zhu, F., Du, B., Bian, Z., & Xu, B. (2015). Beta-glucans from edible and medicinal mushrooms: Characteristics, physicochemical and biological activities. Journal of Food Composition and Analysis, 41, 165–173. https://doi.org/10.1016/j.jfca.2015.01.019

Zi, Y., Jiang, B., He, C., & Liu, L. (2020). Lentinan inhibits oxidative stress and inflammatory cytokine production induced by benzo(a)pyrene in human keratinocytes. Journal of Cosmetic Dermatology, 19(2), 502–507. https://doi.org/10.1111/jocd.13005

Downloads

Published

2024-01-08

Issue

Section

Animal Science