Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Some Wild Mushrooms with High Antioxidant Capacity Exhibit Potent Anticancer Activity on Cancer Cells using the Apoptotic and Antimigration Cell Death Mechanisms

Author(s): Murat Şebin, Necmettin Yılmaz and Ali Aydın*

Volume 23, Issue 13, 2023

Published on: 05 May, 2023

Page: [1567 - 1576] Pages: 10

DOI: 10.2174/1871520623666230331084010

Price: $65

Abstract

Aim: This study aims to provide in vitro experimental evidence that wild mushrooms have the potential to be used as a pharmaceutical that could be effective against various types of cancer.

Background: Throughout human history, besides food, traditional medicine and natural poisons obtained from mushrooms have been used for the treatment of many diseases. Clearly, edible and medicinal mushroom preparations have beneficial health effects without the known severe adverse side effects.

Objectives: This study was designed to reveal the cell growth inhibitory potential of five different edible mushrooms and the biological activity of Lactarius zonarius was shown here for the first time.

Methods: The mushrooms fruiting bodies were dried and powdered then extracted with hexane, ethyl acetate, and methanol. The mushroom extracts were screened for possible antioxidant activities by the free radical scavenging activity (DPPH) method. Antiproliferative activity and cytotoxicity of the extracts were investigated in vitro on A549 (human lung carcinoma), HeLa (human cervix carcinoma), HT29 (human colon carcinoma), Hep3B (human hepatoma), MCF7 (human breast cancer), FL (human amnion cells), and Beas2B (normal human cells) cells lines by using MTT cell proliferation assay, lactate dehydrogenase (LDH) assay, DNA degradation, TUNEL, and cell migration assay.

Results: Using proliferation, cytotoxicity, DNA degradation, TUNEL, and migration assay, we displayed that hexane, ethyl acetate, and methanol extracts of the Lactarius zonarius, Laetiporus sulphureus, Pholiota adiposa, Polyporus squamosus, and Ramaria flava were effective on the cells even so at low doses (< 45.0 - 99.6 µg/mL) by acting in a way that represses migration, as a negative inducer of apoptosis. It was also demonstrated that mushroom extracts with high antioxidant effect have within the acceptable cytotoxic activity of 20%-30% on the cell membrane at concentrations higher than 60 µg/mL.

Overall, all of the mushroom extracts with high antioxidant effects had strong antiproliferative activity and low toxicity for cells. These findings, at least, highlight that these mushroom extracts can be used for the treatment of cancer disease, especially as a supportive therapy against colon, liver, and lung cancer.

Keywords: Lactarius zonarius, anticancer, apoptosis, anti-migration, antioxidant, wild mushrooms.

« Previous Next »
Graphical Abstract

[1]
Miller, K.D.; Nogueira, L.; Mariotto, A.B.; Rowland, J.H.; Yabroff, K.R.; Alfano, C.M.; Jemal, A.; Kramer, J.L.; Siegel, R.L. Cancer treatment and survivorship statistics, 2019. CA Cancer J. Clin., 2019, 69(5), 363-385.
[http://dx.doi.org/10.3322/caac.21565] [PMID: 31184787]
[2]
Wasser, S.P. Medicinal mushroom science: History, current status, future trends, and unsolved problems. Int. J. Med. Mushrooms, 2010, 12(1), 1-16.
[http://dx.doi.org/10.1615/IntJMedMushr.v12.i1.10]
[3]
Chang, S.T.; Wasser, S.P. The role of culinary-medicinal mushrooms on human welfare with a pyramid model for human health. Int. J. Med. Mushrooms, 2012, 14(2), 95-134.
[http://dx.doi.org/10.1615/IntJMedMushr.v14.i2.10] [PMID: 22506573]
[4]
Wu, Y.; Choi, M.H.; Li, J.; Yang, H.; Shin, H-J. Mushroom cosmetics: The present and future. Cosmetics, 2016, 3(3), 22.
[http://dx.doi.org/10.3390/cosmetics3030022]
[5]
Dai, Y.C.; Yang, Z.L.; Cui, B.K.; Yu, C-J.; Zhou, L-W. Species diversity and utilization of medicinal mushrooms and fungi in china: Review. Int. J. Med. Mushrooms, 2009, 11(3), 287-302.
[http://dx.doi.org/10.1615/IntJMedMushr.v11.i3.80]
[6]
Gao, Y.; Zhou, S.; Chen, G.; Dai, X.; Ye, J. A phase I/II study of a Ganoderma lucidum (Curt.: Fr.) P. Karst. Extract (Ganopofy) in patients with advanced cancer. Int. J. Med. Mushrooms, 2002, 4(3), 8.
[http://dx.doi.org/10.1615/IntJMedMushr.v4.i3.30]
[7]
Gao, Y.; Zhou, S.; Huang, M.; Xu, A. Antibacterial and antiviral value of the Genus Ganoderma P. Karst. Species (Aphyllophoromycetideae): A Review. Int. J. Med. Mushrooms, 2003, 5(3), 12.
[http://dx.doi.org/10.1615/InterJMedicMush.v5.i3.20]
[8]
Gao, Y.; Lan, J.; Dai, X.; Ye, J.; Zhou, S. A Phase I/II study of ling zhi mushroom Ganoderma lucidum (W.Curt.:Fr.)lloyd (Aphyllophoromycetideae) extract in patients with type II diabetes mellitus. Int. J. Med. Mushrooms, 2004, 6(1), 8.
[http://dx.doi.org/10.1615/IntJMedMushr.v6.i1.30]
[9]
Wasser, S.P.; Didukh, M.Y. Medicinal value of species of the family agaricaceae cohn (higher basidiomycetes): Current stage of knowledge and future perspectives. Int. J. Med. Mushrooms, 2003, 5(2), 20.
[http://dx.doi.org/10.1615/InterJMedicMush.v5.i2.30]
[10]
Sullivan, R.; Smith, J.E.; Rowan, N.J. Immunomodulatory activities of mushroom glucans and polysaccharide-protein complexes in animals and humans (A Review). Int. J. Med. Mushrooms, 2003, 5(2), 16.
[http://dx.doi.org/10.1615/InterJMedicMush.v5.i2.10]
[11]
Zhang, M.; Cui, S.W.; Cheung, P.C.K.; Wang, Q. Antitumor polysaccharides from mushrooms: A review on their isolation process, structural characteristics and antitumor activity. Trends Food Sci. Technol., 2007, 18(1), 4-19.
[http://dx.doi.org/10.1016/j.tifs.2006.07.013]
[12]
Sharif, S.; Atta, A.; Huma, T.; Shah, A.A.; Afzal, G.; Rashid, S.; Shahid, M.; Mustafa, G. Anticancer, antithrombotic, antityrosinase, and anti-α-glucosidase activities of selected wild and commercial mushrooms from Pakistan. Food Sci. Nutr., 2018, 6(8), 2170-2176.
[http://dx.doi.org/10.1002/fsn3.781] [PMID: 30510718]
[13]
Thu, Z.M.; Myo, K.K.; Aung, H.T.; Clericuzio, M.; Armijos, C.; Vidari, G. Bioactive phytochemical constituents of wild edible mushrooms from Southeast Asia. Molecules, 2020, 25(8), 1972.
[http://dx.doi.org/10.3390/molecules25081972] [PMID: 32340227]
[14]
Kolniak-Ostek, J. Oszmiański, J.; Szyjka, A.; Moreira, H.; Barg, E. Anticancer and antioxidant activities in Ganoderma lucidum wild mushrooms in poland, as well as their phenolic and triterpenoid compounds. Int. J. Mol. Sci., 2022, 23(16), 9359.
[http://dx.doi.org/10.3390/ijms23169359] [PMID: 36012645]
[15]
Datta, H.K.; Das, D.; Koschella, A.; Das, T.; Heinze, T.; Biswas, S.; Chaudhuri, S. Structural elucidation of a heteropolysaccharide from the wild mushroom Marasmiellus palmivorus and its immune-assisted anticancer activity. Carbohydr. Polym., 2019, 211, 272-280.
[http://dx.doi.org/10.1016/j.carbpol.2019.02.011] [PMID: 30824089]
[16]
Lindequist, U. The merit of medicinal mushrooms from a pharmaceutical point of view. Int. J. Med. Mushrooms, 2013, 15(6), 517-523.
[http://dx.doi.org/10.1615/IntJMedMushr.v15.i6.10] [PMID: 24266376]
[17]
Zaidman, B.Z.; Yassin, M.; Mahajna, J.; Wasser, S.P. Medicinal mushroom modulators of molecular targets as cancer therapeutics. Appl. Microbiol. Biotechnol., 2005, 67(4), 453-468.
[http://dx.doi.org/10.1007/s00253-004-1787-z] [PMID: 15726350]
[18]
De Silva, D.D.; Rapior, S.; Sudarman, E.; Stadler, M.; Xu, J.; Aisyah Alias, S.; Hyde, K.D. Bioactive metabolites from macrofungi: Ethnopharmacology, biological activities and chemistry. Fungal Divers., 2013, 62(1), 1-40.
[http://dx.doi.org/10.1007/s13225-013-0265-2]
[19]
Zhang, Y.; Li, S.; Wang, X.; Zhang, L.; Cheung, P.C.K. Advances in lentinan: Isolation, structure, chain conformation and bioactivities. Food Hydrocoll., 2011, 25(2), 196-206.
[http://dx.doi.org/10.1016/j.foodhyd.2010.02.001]
[20]
Lee, D.H.; Kim, H.W. Innate immunity induced by fungal β-glucans via dectin-1 signaling pathway. Int. J. Med. Mushrooms, 2014, 16(1), 1-16.
[http://dx.doi.org/10.1615/IntJMedMushr.v16.i1.10] [PMID: 24940900]
[21]
Guggenheim, A.G.; Wright, K.M.; Zwickey, H.L. Immune modulation from five major mushrooms: Application to integrative oncology. Integr. Med., 2014, 13(1), 32-44.
[PMID: 26770080]
[22]
Zhang, Y.; Kong, H.; Fang, Y.; Nishinari, K.; Phillips, G.O. Schizophyllan: A review on its structure, properties, bioactivities and recent developments. Bio. Carbohyd. Diet. Fibre, 2013, 1(1), 53-71.
[http://dx.doi.org/10.1016/j.bcdf.2013.01.002]
[23]
Petrova, R.D.; Reznick, A.Z.; Wasser, S.P.; Denchev, C.M.; Nevo, E.; Mahajna, J. Fungal metabolites modulating NF-kappaB activity: An approach to cancer therapy and chemoprevention (review). Oncol. Rep., 2008, 19(2), 299-308.
[PMID: 18202775]
[24]
Petrova, R.D.; Mahajna, J.; Wasser, S.P.; Ruimi, N.; Denchev, C.M.; Sussan, S.; Nevo, E.; Reznick, A.Z. Marasmius oreades substances block NF-κB activity through interference with IKK activation pathway. Mol. Biol. Rep., 2009, 36(4), 737-744.
[http://dx.doi.org/10.1007/s11033-008-9237-0] [PMID: 18386159]
[25]
Zaidman, B.Z.; Wasser, S.P.; Nevo, E.; Mahajna, J. Coprinus comatus and Ganoderma lucidum interfere with androgen receptor function in LNCaP prostate cancer cells. Mol. Biol. Rep., 2008, 35(2), 107-117.
[http://dx.doi.org/10.1007/s11033-007-9059-5] [PMID: 17431821]
[26]
Mahajna, J.; Wasser, S.P.; Mahajna, J. Substances from the medicinal mushroom Daedalea gibbosa inhibit kinase activity of native and T315I mutated Bcr-Abl. Int. J. Oncol., 1992, 32(6), 1197-1204.
[http://dx.doi.org/10.3892/ijo_32_6_1197] [PMID: 18497981]
[27]
Rouhana-Toubi, A.; Wasser, S.P.; Fares, F. Ethyl acetate extracts of submerged cultured Mycelium of higher basidiomycetes mushrooms inhibit human ovarian cancer cell Growth. Int. J. Med. Mushrooms, 2009, 11(1), 29-37.
[http://dx.doi.org/10.1615/IntJMedMushr.v11.i1.40]
[28]
Karan, T.; Yildiz, I.; Aydin, A.; Erenler, R. Inhibition of various cancer cells proliferation of bornyl acetate and essential oil from Inula graveolens (Linnaeus). Desf. Rec. Nat. Prod., 2018, 12(3), 273-283.
[http://dx.doi.org/10.25135/rnp.30.17.09.057]
[29]
Blois, M.S. Antioxidant determinations by the use of a stable free radical. Nature, 1958, 181(4617), 1199-1200.
[http://dx.doi.org/10.1038/1811199a0]
[30]
Karadağ A.; Aydın, A.; Dede, S.; Tekin, Ş.; Yanar, Y.; Çadırcı B.H.; Soylu, M.S.; Andaç, Ö. Five novel dicyanidoaurate(I)-based complexes exhibiting significant biological activities: Synthesis, characterization and three crystal structures. New J. Chem., 2015, 39(10), 8136-8152.
[http://dx.doi.org/10.1039/C5NJ01108F]
[31]
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63.
[http://dx.doi.org/10.1016/0022-1759(83)90303-4] [PMID: 6606682]
[32]
Decker, T.; Lohmann-Matthes, M.L. A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J. Immunol. Methods, 1988, 115(1), 61-69.
[http://dx.doi.org/10.1016/0022-1759(88)90310-9] [PMID: 3192948]
[33]
Gong, J.P.; Traganos, F.; Darzynkiewicz, Z. A selective procedure for DNA extraction from apoptotic cells applicable for gel electrophoresis and flow cytometry. Anal. Biochem., 1994, 218(2), 314-319.
[http://dx.doi.org/10.1006/abio.1994.1184] [PMID: 8074286]
[34]
Aydin, A.; Korkmaz, N. Tekin, Ş., Karadağ A. Anticancer activities and mechanism of action of 2 novel metal complexes, C {16} H {34} N {8} O {5} Ag {2} Cd and C {11} H {16} N {7} O {2} Ag {3} Ni. Turk. J. Biol., 2014, 38(6), 948-955.
[http://dx.doi.org/10.3906/biy-1405-68]
[35]
Aydın, A.; Korkmaz, Ş.A.; Demir, V.; Tekin, Ş. Anticancer and cytotoxic activities of [Cu(C6H16N2O [Ni(CN)4] and [Cu(C6H16N2O2Pd(CN)4] cyanidometallate compounds on HT29, HeLa. Anticancer. Agents Med. Chem., 2017, 17(6), 865-874.
[http://dx.doi.org/10.2174/1871520617666170103102417] [PMID: 28044934]
[36]
Gursoy, N.; Sarikurkcu, C.; Tepe, B.; Halil Solak, M. Evaluation of antioxidant activities of 3 edible mushrooms: Ramaria flava (Schaef.: Fr.) Quél., Rhizopogon roseolus (Corda) T.M. Fries., and Russula delica Fr. Food Sci. Biotechnol., 2010, 19(3), 691-696.
[http://dx.doi.org/10.1007/s10068-010-0097-8]
[37]
Ozen, T.; Darcan, C.; Aktop, O.; Turkekul, I. Screening of antioxidant, antimicrobial activities and chemical contents of edible mushrooms wildly grown in the black sea region of Turkey. Comb. Chem. High Throughput Screen., 2011, 14(2), 72-84.
[http://dx.doi.org/10.2174/138620711794474079] [PMID: 20958253]
[38]
Liu, K.; Wang, J.; Zhao, L.; Wang, Q. Anticancer, antioxidant and antibiotic activities of mushroom Ramaria flava. Food Chem. Toxicol., 2013, 58, 375-380.
[http://dx.doi.org/10.1016/j.fct.2013.05.001] [PMID: 23684998]
[39]
Sadi, G.; Kaya, A.; Yalcin, H.A.; Emsen, B.; Kocabas, A.; Kartal, D.I.; Altay, A. Wild Edible Mushrooms from Turkey as possible anticancer agents on HepG2 Cells together with their antioxidant and antimicrobial properties. Int. J. Med. Mushrooms, 2016, 18(1), 83-95.
[http://dx.doi.org/10.1615/IntJMedMushrooms.v18.i1.100] [PMID: 27279448]
[40]
Petrović J.; Glamočlija, J.; Ilić-Tomić T.; Soković M.; Robajac, D.; Nedić O.; Pavić A. Lectin from Laetiporus sulphureus effectively inhibits angiogenesis and tumor development in the zebrafish xenograft models of colorectal carcinoma and melanoma. Int. J. Biol. Macromol., 2020, 148, 129-139.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.01.033] [PMID: 31935408]
[41]
Shi, F.; Fu, Y.; Wang, J.; Li, L.; Wang, A.; Yuan, Y.; Luo, H.; He, H.; Deng, G. Trametenolic acid B triggers HSP90AA4P and autophagy in HepG2/2.2.15 cells by proteomic analysis. ACS Omega, 2020, 5(22), 13042-13051.
[http://dx.doi.org/10.1021/acsomega.0c00962] [PMID: 32548489]
[42]
Wong, J.H.; Ng, T.B.; Chan, H.H.L.; Liu, Q.; Man, G.C.W.; Zhang, C.Z.; Guan, S.; Ng, C.C.W.; Fang, E.F.; Wang, H.; Liu, F.; Ye, X.; Rolka, K.; Naude, R.; Zhao, S.; Sha, O.; Li, C.; Xia, L. Mushroom extracts and compounds with suppressive action on breast cancer: evidence from studies using cultured cancer cells, tumor-bearing animals, and clinical trials. Appl. Microbiol. Biotechnol., 2020, 104(11), 4675-4703.
[http://dx.doi.org/10.1007/s00253-020-10476-4] [PMID: 32274562]
[43]
Zhao, H.; Lan, Y.; Liu, H.; Zhu, Y.; Liu, W.; Zhang, J.; Jia, L. Antioxidant and hepatoprotective activities of polysaccharides from spent mushroom substrates (Laetiporus sulphureus) in acute alcohol-induced mice. Oxid. Med. Cell. Longev., 2017, 2017, 5863523.
[http://dx.doi.org/10.1155/2017/5863523] [PMID: 29430281]
[44]
Khatua, S.; Ghosh, S.; Acharya, K. Laetiporus sulphureus (Bull.: Fr.) Murr. as Food as Medicine. Pharmacogn. J., 2017, 9(6s), s1-s15.
[http://dx.doi.org/10.5530/pj.2017.6s.151]
[45]
Keller, C.; Maillard, M.; Keller, J.; Hostettmann, K. Screening of European fungi for antibacterial, antifungal, larvicidal, molluscicidal, antioxidant and free-radical scavenging activities and subsequent isolation of bioactive compounds. Pharm. Biol., 2002, 40(7), 518-525.
[http://dx.doi.org/10.1076/phbi.40.7.518.14680]
[46]
Wang, M.; Triguéros, V.; Paquereau, L.; Chavant, L.; Fournier, D. Proteins as active compounds involved in insecticidal activity of mushroom fruitbodies. J. Econ. Entomol., 2002, 95(3), 603-607.
[http://dx.doi.org/10.1603/0022-0493-95.3.603] [PMID: 12076007]
[47]
Mocan, A.; Fernandes, Â.; Barros, L. Crişan, G.; Smiljković M.; Soković M.; Ferreira, I.C.F.R. Chemical composition and bioactive properties of the wild mushroom Polyporus squamosus (Huds.) Fr: a study with samples from Romania. Food Funct., 2018, 9(1), 160-170.
[http://dx.doi.org/10.1039/C7FO01514C] [PMID: 29168866]
[48]
Fernandes, Â. Petrović J.; Stojković D.; Barros, L.; Glamočlija, J.; Soković M.; Martins, A.; Ferreira, I.C.F.R. Polyporus squamosus (Huds.) Fr from different origins: Chemical characterization, screening of the bioactive properties and specific antimicrobial effects against Pseudomonas aeruginosa. Lebensm. Wiss. Technol., 2016, 69, 91-97.
[http://dx.doi.org/10.1016/j.lwt.2016.01.037]
[49]
Doskocil, I.; Havlik, J.; Verlotta, R.; Tauchen, J.; Vesela, L.; Macakova, K.; Opletal, L.; Kokoska, L.; Rada, V. In vitro immunomodulatory activity, cytotoxicity and chemistry of some central European polypores. Pharm. Biol., 2016, 54(11), 2369-2376.
[http://dx.doi.org/10.3109/13880209.2016.1156708] [PMID: 26984176]
[50]
Zhang, G.Q.; Sun, J.; Wang, H.X.; Ng, T.B. A novel lectin with antiproliferative activity from the medicinal mushroom Pholiota adiposa. Acta Biochim. Pol., 2009, 56(3), 415-421.
[http://dx.doi.org/10.18388/abp.2009_2475] [PMID: 19636442]
[51]
Hu, Q.; Wang, H.; Ng, T.B. Isolation and purification of polysaccharides with anti-tumor activity from Pholiota adiposa (Batsch) P. Kumm. (higher Basidiomycetes). Int. J. Med. Mushrooms, 2012, 14(3), 271-284.
[http://dx.doi.org/10.1615/IntJMedMushr.v14.i3.40] [PMID: 22577977]
[52]
Zou, Y.; Du, F.; Hu, Q.; Wang, H. The structural characterization of a polysaccharide exhibiting antitumor effect from Pholiota adiposa mycelia. Sci. Rep., 2019, 9(1), 1724.
[http://dx.doi.org/10.1038/s41598-018-38251-6] [PMID: 30741980]
[53]
Wang, C.R.; Zhou, R.; Ng, T.B.; Wong, J.H.; Qiao, W.T.; Liu, F. First report on isolation of methyl gallate with antioxidant, anti-HIV-1 and HIV-1 enzyme inhibitory activities from a mushroom (Pholiota adiposa). Environ. Toxicol. Pharmacol., 2014, 37(2), 626-637.
[http://dx.doi.org/10.1016/j.etap.2014.01.023] [PMID: 24572641]

Rights & Permissions Print Cite
Article Metrics
22
2
© 2024 Bentham Science Publishers | Privacy Policy