Fungal toxins are secondary metabolites, in which many of them were mycotoxins, affecting eukaryotic cells with a broad range of structural and functional variety contributing to the multitude of their classification. This refers to the harmful genotoxic (mutagenic, teratogenic, and carcinogenic) effects of mycotoxins on the one hand, and their cytocidic and antineoplastic properties on the other hand. This “double edged sword” effect could be utilized against the spread of tumors in older patients when the survival is much more important than the mutagenic side effects. To decide which fungal toxins could be used as combined cytotoxic and antimetastatic agents, mycotoxins were divided into three categories: (a) highly genotoxic (mutagenic, teratogenic, and carcinogenic), (b) adversely toxic, and (c) antitumorigenic agents. Highly cytotoxic mycotoxins with tolerable side effects, combined with an antineoplastic character, could be potential candidates against metastasis. From the structure–function relationship of antimetastatic mycotoxins, only general conclusions have been drawn. The presence of ring structures containing heteroatoms, functional groups, and the cumulative presence of oxygen atoms contributed to the oxidative stress and cytotoxicity of mycotoxins. The preselection of mycotoxins excluded category (a), and only the categories (b) and (c) were considered to be potential agents against the metastatic spread of abdominal tumors in rodent metastatic tumor experiments.
-
1.
Steyn, P. S.: Mycotoxins, general view, chemistry and structure. Toxicol Lett 82–83, 843–851 (1995).
-
2.
Milićević, D. R., Skrinjar, M., Baltić, T.: Real and perceived risks for mycotoxin contamination in foods and feeds: Challenges for food safety control. Toxins (Basel) 2, 572–592 (2010).
-
3.
Malir, F., Ostry, V., Pfohl-Leszkowicz, A., Novotna, E.: Ochratoxin A: Developmental and reproductive toxicity – An overview. Birth Defects Res B Dev Reprod Toxicol 98, 493–502 (2013).
-
4.
Marin, S., Ramos, A. J., Cano-Sancho, G., Sanchis, V.: Mycotoxins: Occurrence, toxicology, and exposure assessment. Food Chem Toxicol 60, 218–237 (2013).
-
5.
Heidtmann-Bemvenuti, R., Mendes, G. L., Scaglioni, P. T., Badiale-Furlong, E., Souza-Soares, L. A.: Biochemistry and metabolism of mycotoxins: A review. Afr J Food Sci 5, 861–869 (2011).
-
6.
Pusztahelyi, T., Holb, I. J., Pócsi, I.: Secondary metabolites in fungus-plant interactions. Front Plant Sci 6, 573 (2015).
-
7.
Bräse, S., Encinas, A., Keck, J., Nising, C. F.: Chemistry and biology of mycotoxins and related fungal metabolites. Chem Rev 109, 3903–3990 (2009).
-
8.
Bennett, J. W., Klich, M.: Mycotoxins. Clin Microbiol Rev 16, 497–516 (2003).
-
9.
Hussain, A. M.: Mycotoxins as carcinogens. Basic Life Sci 34, 87–96 (1985).
-
10.
Wang, J. S., Groopman, J. D.: DNA damage by mycotoxins. Mutat Res 424, 167–181 (1999).
-
11.
Wu, Q. H., Wang, X., Yang, W., Nüssler, A. K., Xiong, L. Y., Kuča, K., Dohnal, V., Zhang, X. J., Yuan, Z. H.: Oxidative stress-mediated cytotoxicity and metabolism of T-2 toxin and deoxynivalenol in animals and humans: An update. Arch Toxicol 88, 1309–1326 (2014).
-
12.
Wu, Q., Dohnal, V., Kuca, K., Yuan, Z.: Trichothecenes: Structure-toxic activity relationships. Curr Drug Metab 14, 641–660 (2013).
-
13.
Nascar, S., Chakraverty, R., Ghosh, A.: Mycotoxin: An alternate source of anticancer drug. Int Res J Phamaceut Biosci 2, 31–41 (2015).
-
14.
Kornienko, A., Evidente, A., Vurro, M., Mathieu, V., Cimmino, A., Evidente, M., van Otterlo, W. A., Dasari, R., Lefranc, F., Kiss, R.: Toward a cancer drug of fungal origin. Med Res Rev 35, 937–967 (2015).
-
15.
Essery, J. M., O’Herron, F. A., McGregor, D. N., Bradner, W. T.: Preparation and antitumor activities of some derivatives of 5-methoxysterigmatocystin. J Med Chem 19, 1339–1342 (1976).
-
16.
Claridge, C. A., Bradner, W. T., Schmitz, H.: Antitumor activity of 15-acetoxyscirpen-3, 4-diol. J Antibiot (Tokyo) 31, 485–486 (1978).
-
17.
Claridge, C. A., Schmitz, H.: Production of 3-acetoxyscirpene-4, 15-diol from anguidine (4, 15-diacetoxyscirpene-3-ol) by Fusarium oxysporum f.sp. vasinfectum. Appl Environ Microbiol 37, 693–696 (1979).
-
18.
Kaneko, T., Schmitz, H., Essery, J. M., Rose, W., Howell, H. G., O’Herron, F. A., Nachfolger, S., Huftalen, J., Bradner, W. T., Partyka, R. A., Doyle, T. W., Davies, J., Cundliffe, E.: Structural modifications of anguidine and antitumor activities of its analogs. J Med Chem 25, 579–589 (1982).
-
19.
Bousquet, P. F., Paulsen, L. A., Fondy, C., Lipski, K. M., Loucy, K. J., Fondy, T. P.: Effects of cytochalasin B in culture and in vivo on murine Madison 109 lung carcinoma and on B16 melanoma. Cancer Res 50, 1431–1439 (1990).
-
20.
Seigle-Murandi, F., Steiman, R., Krivobok, S., Beriel, H., Benoit-Guyod, J. L.: Antitumor activity of patulin and structural analogs. Pharmazie 47, 288–291 (1992).
-
21.
Alvi, K. A., Rabenstein, J., Woodard, J., Banker, D. D., Berghold, J. D., Lynch, J., Lieu, K. L., Braude, I. A.: 14′-Hydroxymytoxin B and 1 hydroxyroridin E, two new cytotoxic trichothecenes from Myrothecinm roridum. J Nat Prod 65, 742–744 (2002).
-
22.
Antony, M., Shukla, Y., Janardhanan, K. K.: Protection effect of tenuazonic acid against dimethye benz (a) antracene-induced skin carcinogenesis in mice. Teratog Carcinog Mutagen 22, 309–314 (2002).
-
23.
Han, H. C., Lindequist, U., Hyun, J. W., Kim, Y. H., An, H. S., Lee, D. H., Kim, H. W.: Apoptosis induction by 4beta-acetoxyscirpendiol from Paecilomyces tenuipes in human leukaemia cell lines. Pharmazie 59, 42–49 (2004).
-
24.
Vigushin, D. M., Mirsaidi, N., Brooke, G., Sun, C., Pace, P., Inman, L., Moody, C. J., Coombes, R. C.: Gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with antitumor activity against breast cancer in vivo. Med Oncol 21, 21–30 (2004).
-
25.
Martínez-Luis, S., Cherigo, L., Arnold, E., Spadafora, C., Gerwick, W. H., Cubilla-Rios, L.: Antiparasitic and anticancer constituents of the endophytic fungus Aspergillus sp. Strain F1544. Nat Prod Commun 7, 165–168 (2012).
-
26.
Igarashi, Y., Tabuta, Y., Sekine, A., Fujii, K., Harada, K., Oikawa, T., Sato, M., Furumai, T., Oki, T.: Directed biosynthesis of fluorinated pseurotim A, synerazol and gliotoxin. J Antibiot 57, 748–754 (2004).
-
27.
Wang, T., Zhang, Y., Wang, Y., Pei, Y. H.: Anti-tumor effects of Rubratoxin B on cell toxicity, inhibition of cell proliferation, cytotoxic activity and matrix metalloproteinase-2, 9. Toxicol In Vitro 21, 646–650 (2007).
-
28.
Jow, G. M., Chou, C. J., Chen, B. F., Tsai, J. H.: Beauvericin induces cytotoxic effects in human acute lymphoblastic leukemia cells through cytochrome release, caspase 3 activation: The causative role of calcium. Cancer Lett 216, 165–173 (2004).
-
29.
Sugita-Konishi, Y., Kumagai, S., Mizuochi, T.: The cytotoxicity of macrocyclic trichothecenes, roridin A and verrucarin A, on murine T-cells is reduced by Ia-negative splenic adherent cells. Toxicon 32, 1051–1057 (1994).
-
30.
Choudhury, S. M., Gupta, M., Majumder, U. K.: Antineoplastic activities of MT81 and its structural analog in Ehrlich ascites carcinoma-bearing Swiss Albino mice. Oxid Med Cell Longev 3, 61–70 (2010).
-
31.
Dornetshuber, R., Heffeter, P., Kamyar, M. R., Peterbauer, T., Berger, W., Lemmens-Gruber, R.: Enniatin exerts p53-dependent cytostatic and p53-independent cytotoxic activities against human cancer cells. Chem Res Toxicol 20, 465–473 (2007).
-
32.
Behm, C., Degen, G. H., Föllmann, W.: The Fusarium toxin enniatin B exerts no genotoxic activity, but pronounced cytotoxicity in vitro. Mol Nutr Food Res 53, 423–430 (2009).
-
33.
Tedjiotsop Feudjio, F., Dornetshuber, R., Lemmens, M., Hoffmann, O. R., Lemmens-Gruber, R., Berger, W.: Beauvericin and enniatin: Emerging toxins and/or remedies? World Mycotox J 3, 415–430 (2010).
-
34.
Surai, P. F., Mezes, M., Melnichuk, S. D., Fotina, T. I.: Mycotoxins and animal health: From oxidative stress to gene expression. Krmiva 50, 35–43 (2008).
-
35.
Evidente, A., Kornienko, A., Cimmino, A., Andolfi, A., Lefranc, F., Mathieu, V., Kiss, R.: Fungal metabolites with anticancer activity. Nat Prod Rep 31, 617–627 (2014).
-
36.
Junker, B., Walker, A., Hesse, M., Lester, M., Vesey, D., Christensen, J., Burgess, B., Connors, N.: Pilot-scale process development and scale up for antifungal production. Bioproc Biosyst Engin 32, 443–458 (2009).
-
37.
Heyndrickx, E., Sioen, I., Bellemans, M., De Maeyer, M., Callebaut, A., De Henauw, S., De Saeger, S.: Assessment of mycotoxin exposure in the Belgian population using biomarkers: Aim, design and methods of the BIOMYCO study. Food Addit Contam A 31, 924–931 (2014).
-
38.
Speijers, G. J., Speijers, M. H.: Combined toxic effects of mycotoxins. Toxicol Lett 153, 1–98 (2004).
-
39.
Clarkson, B. D., Burchenal, J. H.: Progress in leukemias. Prog Clin Cancer 1, 625–663 (1965).
-
40.
Wu, F., Groopman, J. D., Pestka, J. J.: Public health impacts of foodborne mycotoxins. Annu Rev Food Sci Technol 5, 351–372 (2014).
-
41.
Sydenham, E. W., Shephard, G. S., Thiel, P. G., Marasas, W. F., Stockenstrom, S.: Fumonisin contamination of commercial corn-based human foodstuffs. J Agric Food Chem 39, 2014–2018 (1991).
-
42.
Madrigal-Santillán, E., Morales-González, J. A., Vargas-Mendoza, N., Reyes-Ramírez, P., Cruz-Jaime, S., Sumaya-Martínez, T., Pérez-Pastén, R., Madrigal-Bujaidar, E.: Antigenotoxic studies of different substances to reduce the DNA damage induced by aflatoxin B(1) and ochratoxin A. Toxins (Basel) 2, 738–757 (2010).
-
43.
Diaz, D. E., Hagler, W. M., Jr., Blackwelder, J. T., Eve, J. A., Hopkins, B. A., Anderson, K. L., Jones, F. T., Whitlow, L. W.: Aflatoxin binders II: Reduction of aflatoxin M1 in milk by sequestering agents of cows consuming aflatoxin in feed. Mycopathologia 157, 233–241 (2004).
-
44.
Galey, F. D., Lambert, R. J., Busse, M., Buck, W. B.: Therapeutic efficacy of superactive charcoal in rats exposed to oral lethal doses of T-2 toxin. Toxicon 25, 493–499 (1987).
-
45.
Harvey, R. B., Kubena, L. F., Phillips, T. D., Huff, W. E., Corrier, D. E.: Prevention of aflatoxicosis by addition of hydrated sodium calcium aluminosilicate to the diets of growing barrows. Am J Vet Res 50, 416–420 (1989)
-
46.
Lindemann, M. D., Blodgett, D. J.: Various clays provide alternative for dealing with Aflatoxin. Feedstuffs 63, 15–29 (1991).
-
47.
Scheideler, S. E.: Aluminosilicates in poultry rations. Feed Manage 41, 22, 24–26 (1990).
-
48.
Hayes, S. M.: Counteracting aflatoxin in livestock feed. Agricultural Research USDA, ARS, Washington, DC, 1990, 38, p. 18.
-
49.
Smith, T. K.: Influence of dietary fiber, protein and zeolite on zearalenone toxicosis in rats and swine. J Anim Sci 50, 278 (1980).
-
50.
Gerhards, N., Neubauer, L., Tudzynski, P., Li, S. M.: Biosynthetic pathways of ergot alkaloids. Toxins (Basel) 6, 3281–3295 (2014).
-
51.
Eadie, M. J.: Convulsive ergotism: Epidemics of the serotonin syndrome? Lancet Neurol 2, 429–434 (2003).
-
52.
Tsuchimoto, T., Stalder, G. R.: Effect of an ergot derivative on human lymphocyte chromosomes in vivo. Drug Res 26, 2101–2103 (1976).
-
53.
Tsuchimoto, T., Matter, B. E., Deyssenroth, H.: Analysis of chromosome aberrations and sister chromatid exchanges in human lymphocytes exposed in vitro to Hydergine R. Mutation Res 67, 39–45 (1979).
-
54.
Matter, B. E., Tsuchimoto, T., Deyssenroth, H.: Failure to detect dominant-lethal mutations and effects on reproductive capacity in mice exposed to dihydroergotoxine mesylate. Drug Res 28, 2286–2290 (1978).
-
55.
Matter, B. E.: Heritable translocation test in mice with triethylenemelamine (TEM) and ergotamine. Mutation Res 104, 177–182 (1982).
-
56.
Roberts, G. T., Rand, M. J.: Chromosomal damage induced by some ergot derivatives in vitro. Mutation Res 48, 205–214 (1977a).
-
57.
Roberts, G. T., Rand, M. J.: Effects of some ergot derivatives in bone-marrow of mice. Mutation Res 56, 59–68 (1977b).
-
58.
Alexander, J., Benford, D., Boobis, A., Ceccatelli, S., Cottrill, B., Cravedi, J.-P., Di Domenico, A., Doerge, D., Dogliotti, E., Edler, L., Farmer, P., Filipič, M., Fink-Gremmels, J., Fürst, P., Guérin, T., Knutsen, H. K., Machala, M., Mutti, A., Rose, M., Schlatter, J., van Leeuwen, R.: Scientific opinion on ergot alkaloids in food and feed. Panel on contaminants in the food chain. Eur Food Safe Auth J 10, 2798 (2012).
-
59.
Eich, E., Eichberg, D., Müller, W. E.: Clavines. New antibiotics with cytostatic activity. Biochem Pharmacol 33, 523–526 (1984).
-
60.
Holzapfel, C. W.: The isolation and structure of cyclopiazonic acid, a toxic metabolite of Penicillium cyclopium westling. Tetrahedron 24, 2101–2119 (1968).
-
61.
Plenge-Tellechea, F., Soler, F., Fernandez-Belda, F.: On the inhibition mechanism of sarcoplasmic or endoplasmic reticulum Ca2+-ATPases by cyclopiazonic acid. J Biol Chem 272, 2794–2800 (1997).
-
62.
Cole, R. J., Cox, R. H.: The trichothecenes. In Cole, R. J., Cox, R. H. (eds): Handbook of Toxic Fungal Metabolites. Academic Press, New York, NY, 1981, pp. 152–263.
-
63.
Scott, P. M.: The natural occurrence of trichothecenes. In Beasley, V. R. (ed): Trichothecene Mycotoxicosis: Pathophysiologic Effects. CRC Press, Boca Raton, FL, USA, 1989, pp. 1–26.
-
64.
Ueno, Y. (ed): Trichothecenes: Chemical, Biological and Toxicological Aspects. Elsevier, Amsterdam, The Netherlands, 1983.
-
65.
McCormick, S. P., Stanley, A. M., Stover, N. A., Alexander, N. J.: Trichothecenes: From simple to complex mycotoxins. Toxins (Basel) 3, 802–814 (2011).
-
66.
Yoshizawa, T., Jin, Y. Z.: Natural occurrence of acetylated derivatives of deoxynivalenol in wheat and barley in Japan. Food Addit Contam 12, 689–694 (1995).
-
67.
Li, Y., Wang, Z., Beier, R. C., Shen, J., De Smet, D., De Saeger, S, Zhang, S.: T-2 toxin, a trichothecene mycotoxin: Review of toxicity, metabolism, and analytical methods. J Agric Food Chem 59, 3441–3453 (2011).
-
68.
Ramu, A., Yagen, B., Ramu, N.: The cytotoxicity of T-2 toxin and related 12, 13-epoxytrichothecenes to Adriamycin-sensitive and -resistant P388 leukemia cells. Canc Chemother Pharmacol 24, 264–267 (1989).
-
69.
Weidner, M., Welsch, T., Hübner, F., Schwerdt, G., Gekle, M., Humpf, H. U.: Identification and apoptotic potential of T-2 toxin metabolites in human cells. J Agric Food Chem 60, 5676–5684 (2012).
-
70.
Wu, Q., Dohnal, V., Huang, L., Kuca, K., Yuan, Z.: Metabolic pathways of trichothecenes. Drug Metab Rev 42, 250–267 (2010).
-
71.
Meselson, M. S., Robinson, J. P.: The yellow rain affair: Lessons from a discredited allegation. In Clunan, A. L., Lavoy, P. R., Martin, S. B. (eds): Terrorism, War, or Disease? Unraveling the Use of Biological Weapons. Stanford University Press, Stanford, 2008, pp. 72–96.
-
72.
Nielsen, C., Casteel, M., Didier, A., Dietrich, R., Märtlbauer, E.: Trichothecene-induced cytotoxicity on human cell lines. Mycotoxin Res 25, 77–84 (2009).
-
73.
Nusuetrong, P., Saito, M., Kikuchi, H., Oshima, Y., Moriya, T., Nakahata, N.: Apoptotic effects of satratoxin H is mediated through DNA double-stranded break in PC12 cells. J Toxicol Sci 37, 803–812 (2012).
-
74.
Nusuetrong, P., Pengsuparp, T., Meksuriyen, D., Tanitsu, M., Kikuchi, H., Mizugaki, M., Shimazu, K., Oshima, Y., Nakahata, N., Yoshida, M.: Satratoxin H generates reactive oxygen species and lipid peroxides in PC12 cells. Biol Pharm Bull 31, 1115–1120 (2008).
-
75.
Brian, P. W., Dawkins, A. W., Grove, J. F., Hemming, H. G., Lowe, D., Norris, G. L. F.: Phytotoxic compounds produced by Fusarium equiseti. J Exp Bot 12, 1–12 (1961).
-
76.
Claridge, C. A., Schmitz, H., Bradner, W. T.: Antitumor activity of some microbial and chemical transformation products of anguidine (4,15-diacetoxyscirpene-3-ol). Cancer Chemother Pharmacol 2, 181–182 (1979).
-
77.
Haas, C. D., Goodwin, J. W., Leite, C. J., Stephens, R. L., Hoogstraten, B.: Phase I studies of anguidine (diacetoxyscirpenol NSC 141537). Proc Am Assoc Cancer Res 18, 296 (1977).
-
78.
Murphy, W. K., Burgess, M. A., Valdivieso, M., Livingston, R. B., Bodey, G. P., Freireich, E. J.: Phase I evaluation of anguidine. Cancer Treat Rep 62, 1497–1502 (1978).
-
79.
Dosik, G. M., Barlogie, B., Johnston, D. A., Murphy, W. K., Drewinko, B.: Lethal and cytokinetic effects of anguidine on a human colon cancer cell line. Cancer Res 38, 3304–3309 (1978).
-
80.
Teodori, L., Barlogie, B., Drewinko, B., Swartzendruber, D., Mauro, F.: Reduction of 1-/S-D-arabinofuranosylcytosine and Adriamycin cytotoxicity following cell cycle arrest by anguidine. Cancer Res 41, 1263–1270 (1981).
-
81.
Hromas, R., Barlogie, B., Drewinko, B., Ho, D. H. W.: Differential cell cycle arrest of normal versus transformed cells by the protein synthesis inhibitor anguidine. Proc Am Assoc Cancer Res 23, 206 (1982).
-
82.
Ember, L. R.: Yellow rain. Chem Engin News 62, 8–34 (1984).
-
83.
Ueno, Y.: Trichothecene mycotoxins: Mycology, chemistry, and toxicology. Adv Nutr Res 3, 301–353 (1989).
-
84.
Wannemacher, R. W., Jr., Bunner, D. L., Neufeld, H. A.: Toxicity of trichothecenes and other related mycotoxins in laboratory animals. In Smith, J. E., Henderson R. S. (eds): Mycotoxins and Animal Foods. CRC Press, Boca Raton, FL, 1991, pp. 499–552.
-
85.
Westlake, K., Mackie, R. I., Dutton, M. F.: T-2 toxin metabolism by ruminal bacteria and its effect on their growth. Appl Environ Microbiol 53, 587–592 (1987).
-
86.
Swanson, S. P., Helaszek, C., Buck, W. B., Rood, H. D. J., Haschek, W. M.: The role of intestinal microflora in the metabolism of trichothecene mycotoxins. Food Chem Toxicol 26, 823–830 (1998).
-
87.
Yoshizawa, T., Sakamoto, T., Okamkoto, K.: In vitro formation of 3′-hydroxy T-2 and 3′-hydroxy HT-2 toxins from T-2 toxin by liver homogenates from mice and monkeys. Appl Environ Microbiol 47, 130–134 (1984).
-
88.
Ghareeb, K., Awad, W. A., Böhm, J., Zebeli, Q.: Impacts of the feed contaminant deoxynivalenol on the intestine of monogastric animals: Poultry and swine. J Appl Toxicol 35, 327–337 (2015).
-
89.
Williams, K. C., Blaney, B. J., Magee, M. H.: Responses of pigs fed wheat naturally infected with fusarium graminearum and containing the mycotoxins 4-deoxynivalenol and zearalenone. Aust J Agric Res 39, 1095–1105 (1988).
-
90.
Richard, J. L.: Some major mycotoxins and their mycotoxicoses: An overview. Int J Food Microbiol 119, 3–10 (2007).
-
91.
Chen, F., Ma, Y., Xue, C., Ma, J., Xie, Q., Wang, G., Bi, Y., Cao, Y.: The combination of deoxynivalenol and zearalenone at permitted feed concentrations causes serious physiological effects in young pigs. J Vet Sci 9, 39–44 (2008).
-
92.
Chaytor, A. C., See, M. T., Hansen, J. A., de Souza, A. L., Middleton, T. F., Kim, S. W.: Effects of chronic exposure of diets with reduced concentrations of aflatoxin and deoxynivalenol on growth and immune status of pigs. J Anim Sci 89, 124–135 (2011).
-
93.
Weaver, A. C., See, M. T., Kim, S. W.: Protective effect of two yeast based feed additives on pigs chronically exposed to deoxynivalenol and zearalenone. Toxins (Basel) 6, 3336–3353 (2014).
-
94.
Mishra, S., Dwivedi, P. D., Pandey, H. P., Das, M.: Role of oxidative stress in deoxynivalenol induced toxicity. Food Chem Toxicol 72, 20–29 (2014).
-
95.
Wang, Z., Wu, Q., Kuča, K., Dohnal, V., Tian, Z.: Deoxynivalenol: Signaling pathways and human exposure risk assessment – An update. Arch Toxicol 88, 1915–1928 (2014).
-
96.
Cortinovis, C, Pizzo, F, Spicer, L. J., Caloni, F.: Fusarium mycotoxins: Effects on reproductive function in domestic animals – A review. Theriogenology 80, 557–564 (2013).
-
97.
Siegel, D., Feist, M., Proske, M., Koch, M., Nehls, I.: Degradation of the Alternaria mycotoxins alternariol, alternariol monomethyl ether, and altenuene upon bread baking. J Agric Food Chem 58, 9622–9630 (2010).
-
98.
Schreck, I., Deigendesch, U., Burkhardt, B., Marko, D., Weiss, C.: The Alternaria mycotoxins alternariol and alternariol methyl ether induce cytochrome P450 1A1 and apoptosis in murine hepatoma cells dependent on the aryl hydrocarbon receptor. Arch Toxicol 86, 625–632 (2012).
-
99.
Maiya, S., Grundmann, A., Li, X., Li, S. M., Turner, G.: Identification of a hybrid PKS/NRPS required for pseurotin A biosynthesis in the human pathogen Aspergillus fumigatus. Chem Bio Chem 8, 1736–1743 (2007).
-
100.
Vödisch, M., Scherlach, K., Winkler, R., Hertweck, C., Braun, H. P., Roth, M., Haas, H., Werner, E. R., Brakhage, A. A., Kniemeyer, O.: Analysis of the Aspergillus fumigatus proteome reveals metabolic changes and the activation of the pseurotin A biosynthesis gene cluster in response to hypoxia. J Proteome Res 10, 2508–2524 (2011).
-
101.
Schmeda-Hirschmann, G., Hormazabal, E., Rodriguez, J. A., Theoduloz, C.: Cycloaspeptide A and pseurotin A from the endophytic fungus Penicillium janczewskii. Z Naturforsch C 63, 383–388 (2008).
-
102.
Ishikawa, M., Ninomiya, T., Akabane, H., Kushida, N., Tsujiuchi, G., Ohyama, M., Gomi, S., Shito, K., Murata, T.: Pseurotin A and its analogues as inhibitors of immunoglobuline E production. Bioorg Med Chem Lett 19, 1457–1460 (2009).
-
103.
Ando, O., Satake, H., Nakajima, M., Sato, A., Nakamura, T., Kinoshita, T., Furuya, K., Haneishi, T.: Synerazol, a new antifungal antibiotic. J Antibiot (Tokyo) 44, 382–389 (1991).
-
104.
Mori, N., Ishikawa, C., Uchihara, J. N., Yasumoto, T.: Protein phosphatase 2A as a potential target for treatment of adult T cell leukemia. Curr Cancer Drug Targets 13, 829–842 (2013).
-
105.
Wada, S., Usami, I., Umezawa, Y., Inoue, H., Ohba, S., Someno, T., Kawada, M., Ikeda, D.: Rubratoxin A specifically and potently inhibits protein phosphatase 2A and suppresses cancer metastasis. Cancer Sci 101, 743–750 (2010).
-
106.
Fimiani, V., Richetti, A.: Antitumor effect of a mycotoxin: Rubratoxin B. Chemotherapy 39, 59–62 (1993).
-
107.
Logrieco, A., Moretti, A., Castella, G., Kostecki, M., Golinski, P., Ritieni, A., Chelkowski, J.: Beauvericin production by Fusarium species. Appl Environ Microbiol 64, 3084–3088 (1998).
-
108.
Logrieco, A., Moretti, A., Ritieni, A., Caraffa, M. F., Macchia, L.: Beauvericin: Chemistry, biology and significance. In Upadhyay, R. K. (ed): Advances in Microbial Toxin Research and its Biotechnological Exploitation. Elsevier Science Publishers, Amsterdam, The Netherlands, 2001.
-
109.
Ojcious, D. M., Zychlinsky, A., Zheng, L. M., Young, J. D.: Ionophore-induced apoptosis: Role of DNA fragmentation and calcium fluxes. Exp Cell Res 197, 43–49 (1991).
-
110.
Logrieco, A., Rizzo, A., Ferracane, R., Ritieni, A.: Occurrence of beauvericin and enniatins in wheat affected by Fusarium avenaceum head blight. Appl Environ Microbiol 68, 82–85 (2002).
-
111.
Zhan, J., Burns, A. M., Liu, M. X., Faeth, S. H., Gunatilaka, A. A. L.: Search for cell motility and angiogenesis inhibitors with potential anticancer activity: Beauvericin and other constituents of two endophytic strains of Fusarium oxysporum. J Nat Prod 70, 227–232 (2007).
-
112.
Tao, Y. W., Lin, Y. C., She, Z. G., Lin, M. T., Chen, P. X., Zhang, J. Y.: Anticancer activity and mechanism investigation of beauvericin isolated from secondary metabolites of the mangrove endophytic fungi. Anticancer Agents Med Chem 15, 258–266 (2015).
-
113.
Ovchinnikov, Y. A., Ivanov, V. T., Evstratov, A. V., Mikhaleva, I. I., Bystrov, V. F., Portnova, S. L., Balashova, T. A., Meshcheryakova, E. N., Tulchinsky, V. M.: Enniatin ionophores. Conformation and ion binding properties. Internat J Pept Prot Res 6, 465–498 (1974).
-
114.
Wätjen, W., Debbab, A., Hohlfeld, A., Chovolou, Y., Kampkötter, A., Edrada, R. A., Ebel, R., Hakiki, A., Mosaddak, M., Totzke, F., Kubbutat, M. H., Proksch, P.: Enniatins A1, B and B1 from an endophytic strain of Fusarium tricinctum induce apoptotic cell death in H4IIE hepatoma cells accompanied by inhibition of ERK phosphorylation. Mol Nutr Food Res 53, 431–440 (2009).
-
115.
Dornetshuber-Fleiss, R., Heilos, D., Mohr, T., Richter, L., Süssmuth, R. D., Zlesak, M., Novicky, A., Heffeter, P., Lemmens-Gruber, R., Berger, W.: The naturally born fusariotoxin enniatin B and sorafenib exert synergistic activity against cervical cancer in vitro and in vivo. Biochem Pharmacol 93, 318–331 (2015).
-
116.
Frisvad, J. C., Thrane, U., Samson, R. A., Pitt, J. I.: Important mycotoxins and the fungi which produce them. In Hocking, A. D., Pitt, J. I., Samson, R. A., Thrane, U. (eds): Advances in Food Mycology. Springer Science + Business Media, Inc., New York, NY, 2006, p. 23.
-
117.
Arora, D. K., Arora, K.: Fungal Biotechnology in Agricultural, Food, and Environmental Applications. Marcel Dekker Inc., New York, 2003, pp. 336.
-
118.
Cooper, J. A.: Effects of cytochalasin and phalloidin on actin. J Cell Biol 105, 1473–1478 (1987).
-
119.
Van Goietsenoven, G., Mathieu, V., Andolfi, A., Cimmino, A., Lefranc, F., Kiss, R., Evidente, A.: In vitro growth inhibitory effects of cytochalasins and derivatives in cancer cells. Planta Med 77, 711–717 (2011).
-
120.
Carter, S. B.: Effects of cytochalasins on mammalian cells. Nature 213, 261–264 (1967).
-
121.
Alcorn, J. L.: The taxonomy of “Heminthosporium” species. Annu Rev Phytopathol 26, 37–56 (1988).
-
122.
Masi, M., Meyerm, S., Cimminom, A., Andolfi, A., Evidente, A.: Pyrenophoric acid, a phytotoxic sesquiterpenoid penta-2, 4-dienoic acid produced by a potential mycoherbicide, Pyrenophora semeniperda. J Nat Prod 77, 925–930 (2014).
-
123.
Sugimura, S., Kawahara, M., Wakai, T., Yamanaka, K., Sasada, H., Sato, E.: Effect of cytochalasins B and D on the developmental competence of somatic cell nuclear transfer embryos in miniature pigs. Zygote 16, 53–59 (2008).
-
124.
Trendowski, M.: Using cytochalasins to improve current chemotherapeutic approaches. Anticancer Agents Med Chem 15, 327–335 (2015).
-
125.
Trendowski, M., Wong, V., Yu, G., Fondy, T. P.: Enlargement and multinucleation of u937 leukemia and MCF7 breast carcinoma cells by antineoplastic agents to enhance sensitivity to low frequency ultrasound and to DNA-directed anticancer agents. Anticancer Res 35, 65–76 (2015).
-
126.
Trendowski, M., Mitchell, J. M., Corsette, C. M., Acquafondata, C., Fondy, T. P.: Chemotherapy in vivo against M109 murine lung carcinoma with cytochalasin B by localized, systemic, and liposomal administration. Invest New Drugs 33, 280–289 (2015a).
-
127.
Huang, F. Y., Li, Y. N., Mei, W. L., Dai, H. F., Zhou, P., Tan, G. H.: Cytochalasin D, a tropical fungal metabolite, inhibits CT26 tumor growth and angiogenesis. Asian Pac J Trop Med 5, 169–174 (2012).
-
128.
Huang, F. Y., Mei, W. L., Tan, G. H., Dai, H. F., Li, Y. N., Guo, J. L., Huang, Y. H., Zhao, H. G., Wang, H., Zhou, S. L., Lin, Y. Y.: Cytochalasin D promotes pulmonary metastasis of B16 melanoma through expression of tissue factor. Oncol Rep 30, 478–484 (2013).
-
129.
Zhang, D., Ge, H., Xie, D., Chen, R., Zou, J. H., Tao, X., Dai, J.: Periconiasins A-C, new cytotoxic cytochalasans with an unprecedented 9/6/5 tricyclic ring system from endophytic fungus Periconia sp. Org Lett 15, 1674–1677 (2013).
-
130.
Ding, G., Wang, H., Li, L., Song, B., Chen, H., Zhang, H., Liu, X., Zou, Z.: Trichodermone, a spiro-cytochalasan with a tetracyclic nucleus (7/5/6/5) skeleton from the plant endophytic fungus Trichoderma gamsii. J Nat Prod 77, 164–167 (2014).
-
131.
Li, X. G., Pan, W. D., Lou, H. Y., Liu, R. M., Xiao, J. H., Zhong, J. J.: New cytochalasins from medicinal macrofungus Crodyceps taii and their inhibitory activities against human cancer cells. Bioorg Med Chem Lett 25, 1823–1826 (2015).
-
132.
Gebhardt, K., Schimana, J., Höltzel, A., Dettner, K., Draeger, S., Beil, W., Rheinheimer, J., Fiedler, H. P.: Aspochalamins A-D and aspochalasin Z produced by the endosymbiotic fungus Aspergillus niveus LU 9575. I. Taxonomy, fermentation, isolation and biological activities. J Antibiot (Tokyo) 57, 707–714 (2004).
-
133.
Gupta, M., Chatterjee, T., Sengupta, S., Majumder, S. K.: Structure of a new mycotoxin (MT81). Indian J Chem 13, 393 (1984).
-
134.
Gupta, M., Chatterjee, T., Dey, S. N., Majumder, S. K.: Effect of a new mycotoxin (MT81) from Penicillium nigricans on liver function in mice. Indian Drugs 19, 430 (1982).
-
135.
Gupta, M., Majumdar, U. K., Ray, M. R., Mukhopadhay, D. K.: Inhibition of experimental murine tumors by MT81, a new mycotoxin from Penicillium nigricans. Neoplasma 44, 329–333 (1997).
-
136.
Peto, J.: Cancer epidemiology in the last century and the next decade. Nature 411, 390–395 (2001).
-
137.
Choudhury, S. M., Rana, M. P., Chatterjee, T. K., Mazumder, U. K., Gupta, M.: Antimicrobial activities of mycotoxin MT81 and its structural derivatives. Indian J Exp Biol 30, 140–141 (1992).
-
138.
Mizutani, K., Kumagai, S., Mochizuki, N., Kitagawa, Y., Sugita-Konishi, Y.: Determination of a yellow rice toxin, luteoskyrin, in rice by using liquid chromatography-tandem mass spectrometry with electrospray ionization. J Food Prot 72, 1321–1326 (2009).
-
139.
Finoli, C., Vecchio, A., Galli, A., Dragoni, I.: Roquefortine C occurrence in blue cheese. J Food Prot 64, 246–251 (2001).
-
140.
Borthwick, A. D., Da Costa, N. C.: 2,5-diketopiperazines in food and beverages: Taste and bioactivity. Crit Rev Food Sci Nutr 57, 718–742 (2017).
-
141.
Aninat, C., André, F., Delaforge, M.: Oxidative metabolism by P450 and function coupling to efflux systems: Modulation of mycotoxin toxicity. Food Addit Contam 22, 361–368 (2005).
-
142.
Bradner, W. T., Bush, J. A., Myllymaki, R. W., Nettleton, D. E., Jr., O’herron, F. A.: Fermentation, isolation, and antitumor activity of sterigmatocystins. Antimicrob Agents Chemother 8, 159–163 (1975).
-
143.
Gosio, B.: Bacteriological and chemical research on maize alterations. Rivista Igiene Sanita Pub Ann 7, 825–868 (1896).
-
144.
Alsberg, C. L., Black, O. F.: Contribution to the study of maize deterioration. US Dept Agric Bureau Plant Ind Bull 270, 7–48 (1913).
-
145.
Lintrup, J., Hyltoft-Petersen, P., Knudtzon, S., Nissen, N. I.: Metabolic studies in man with mycophenolic acid (NSC-129185), a new antitumor agent. Cancer Chemother Rep 56, 229–235 (1972).
-
146.
Knudtzon, S., Nissen, N. I.: Clinical trial with mycophenolic acid (NSC-129185), a new antitumor agent. Cancer Chemother Rep 56, 221–227 (1972).
-
147.
Brewin, T. B., Cole, M. P., Jones, C. T., Platt, D. S., Todd, I. D.: Mycophenolic acid (NSC-129185): Preliminary clinical trials. Cancer Chemother Rep 56, 83–87 (1972).
-
148.
Kitchin, J. E., Pomeranz, M. K., Pak, G., Washenik, K., Shupack, J. L.: Rediscovering mycophenolic acid: A review of its mechanism, side effects, and potential uses. J Am Acad Dermatol 37, 445–449 (1997).
-
149.
Williams, R. H., Lively, D. H., Delong, D. C., Cline, J. C., Sweeney, M. J., Poore, G. A., Larsan, S. M.: Mycophenolic acid: Antiviral and antitumor properties. J Antibiot 21, 463–464 (1968).
-
150.
Sweeney, K. G., Harris, P. N., Holmes, R. E., Poore, G. A., Williams, R. H.: Experimental antitumor activity and preclinical toxicology of mycophenolic acid. Cancer Res 32, 1795–1802 (1972).
-
151.
Ohsugi, Y., Suzuki, S., Takagaki, Y.: Antitumor and immunosuppressive effects of mycophenolic acid derivatives. Cancer Res 36, 2923–2927 (1976).
-
152.
Alexander, P.: Prospects for immunotherapy of cancer: Experience in experimental systems. Brit Med J 4, 484–486 (1970).
-
153.
Jones, D. F., Mills, S. D.: Preparation and antitumor properties of analogs and derivatives of mycophenolic acid. J Med Chem 14, 305–311 (1971).
-
154.
Domhan, S., Muschal, S., Schwager, C., Morath, C., Wirkner, U., Ansorge, W., Maercker, C., Zeier, M., Huber, P. E., Abdollahi, A.: Molecular mechanisms of the antiangiogenic and antitumor effects of mycophenolic acid. Mol Cancer Ther 7, 1656–1668 (2008).
-
155.
Dun, B., Xu, H., Sharma, A., Liu, H., Yu, H., Yi, B., Liu, X., He, M., Zeng, L., She, J. X.: Delineation of biological and molecular mechanisms underlying the diverse anticancer activities of mycophenolic acid. Int J Clin Exp Pathol 6, 2880–2886 (2013).
-
156.
Rodríguez-Pascual, J., Sha, P., García-García, E., Rajeshkumar, N. V., De Vicente, E., Quijano, Y., Cubillo, A., Angulo, B., Hernando, O., Hidalgo, M.: A preclinical and clinical study of mycophenolate mofetil in pancreatic cancer. Invest New Drugs 31, 14–19 (2013).
-
157.
Majd, N., Sumita, K., Yoshino, H., Chen, D., Terakawa, J., Daikoku, T., Kofuji, S., Curry, R., Wise-Draper, T. M., Warnick, R. E., Guarnaschelli, J., Sasaki, A. T.: A review of the potential utility of mycophenolate mofetil as a cancer therapeutic. J Cancer Res 2014, 423401 (2014).
-
158.
Baughman, R. P., Lower, E. E.: Treatment of sarcoidosis. Clin Rev Allergy Immunol 49, 79–92 (2015).
-
159.
Moravan, M., Segal, B. M.: Treatment of CNS sarcoidosis with infliximab and mycophenolate mofetil. Neurology 72, 337–40 (2009).
-
160.
Brill, A. K., Ott, S. R., Geiser, T.: Effect and safety of mycophenolate mofetil in chronic pulmonary sarcoidosis: A retrospective study. Respiration 86, 376–83 (2013).
-
161.
Hamzeh, N., Voelker, A., Forssén, A., Gottschall, E. B., Rose, C., Mroz, P., Maier, L. A.: Efficacy of mycophenolate mofetil in sarcoidosis. Respir Med 108, 1663–1669 (2014).
-
162.
Felczak, K., Vince, R., Pankiewicz, K. W.: NAD-based inhibitors with anticancer potential. Bioorg Med Chem Lett 24, 332–336 (2014).
-
163.
Sunohara, K., Mitsuhashi, S., Shigetomi, K., Ubukata, M.: Discovery of N-(2,3,5-triazoyl)mycophenolic amide and mycophenolic epoxyketone as novel inhibitors of human IMPDH. Bioorg Med Chem Lett 23, 5140–5144 (2013).
-
164.
Phillips, N. J., Goodwin, J. T., Fraiman, A., Cole, R. J., Lynn, D. G.: Characterization of the Fusarium toxin equisetin: The use of phenylboronates in structure assignment. J Am Chem Soc 111, 8223–8231 (1989).
-
165.
Hazuda, D., Blau, C. U., Felock, P., Hastings, J., Pramanik, B., Wolfe, A., Bushman, F., Farnet, C., Goetz, M., Williams, M., Silverman, K., Lingham, R., Singh, S.: Isolation and characterization of novel human immunodeficiency virus integrase inhibitors from fungal metabolites. Antivir Chem Chemother 10, 63–70 (1999).
-
166.
Suzuki, S., Kimura, T., Saito, F., Ando, K.: Antitumor and antiviral properties of penicillic acid. Agric Biol Chem 35, 287–290 (1971).
-
167.
Gomes, N. G. M., Lefran, C. F., Kijjoa, A., Kiss, R.: Can some marine-derived fungal metabolites become actual anticancer agents? Marine Drugs 13, 3950–3991 (2015).
-
168.
Newman, D. J., Cragg, G. M.: Drugs and drug candidates from marine sources: An assessment of the current “state of play”. Planta Medica 82, 775–789 (2016).
-
169.
Adpressa, D. A., Loesgen, S.: Bioprospecting chemical diversity and bioactivity in a marine derived Aspergillus terreus. Chem Biodivers 13, 253–259 (2016).
-
170.
Matsunaga, S., Fusetani, N., Kato, Y., Hirota, H.: Aurantosides A and B: Cytotoxic tetramic acid glycosides from the marine sponge Theonella sp. J Am Chem Soc 113, 9690–9692 (1991).
-
171.
Sata, N. U., Matsunaga, S., Fusetani, N., van Soest, R. W.: Aurantosides D, E, and F: New antifungal tetramic acid glycosides from the marine sponge Siliquariaspongia japonica. J Nat Prod 62, 969–971 (1999).
-
172.
Wang, J., Wang, Z., Ju, Z., Wan, J., Liao, S., Lin, X., Zhang, T., Zhou, X., Chen, H., Tu, Z., Liu, Y.: Cytotoxic cytochalasins from marine-derived fungus Arthrinium arundinis. Planta Med 81, 160–166 (2015).
-
173.
Liu, G., Gu, Q., Zhu, W., Cui, C., Fan, G., Fang, Y., Zhu, T., Liu, H.: 10-Phenyl-[12]-cytochalasins Z7, Z8, and Z9 from the marine-derived fungus Spicaria elegans. J Nat Prod 69, 871–875 (2006).
-
174.
Yan, B.-C., Wang, W.-G., Hu, D.-B., Sun, X., Kong, L.-M., Li, X.-N., Du, X., Luo, S.-H., Liu, Y., Li, Y., Sun, H.-D., Pu, J.-X.: Phomopchalasins A and B, two cytochalasans with polycyclic-fused skeletons from the endophytic ungus Phomopsis sp. shj2. Org Lett 18, 1108–1111 (2016).
-
175.
Newman, D. J.: Natural products as leads to potential drugs: An old process or the new hope for drug discovery? J Med Chem 51, 2589–2599 (2008).
-
176.
Cragg, G. M., Grothaus, P. G., Newman, D. J.: New horizons for old drugs and drug leads. J Nat Prod 77, 703–723 (2014).
-
177.
Omar, H. E.: Mycotoxins-induced oxidative stress and disease. In Makun, H. A. (ed): Mycotoxin and food safety in developing countries. Intech Open Science, Rijeka, Croatia, 2013.
-
178.
Wu, Q., Dohnal, V., Kuca, K., Yuan, Z.: Trichothecenes: Structure-toxic activity relationships. Curr Drug Metab 14, 641–660 (2013).
-
179.
Paterlini-Brechot, P., Benali, N. L.: Circulating tumor cells (CTC) detection: Clinical impact and future directions. Cancer Lett 253, 180–204 (2007).
-
180.
Banfalvi, G.: Role of parathymic lymph nodes in metastatic tumor development. Cancer Metast Rev 31, 89–97 (2012a).
-
181.
Rozsa, D., Trencsenyi, G., Kertai, P., Marian, T., Nagy, G., Banfalvi, G.: Lymphatic spread of mesenchymal renal tumor to metastatic parathymic lymph nodes. Histol Histopathol 24, 1367–1379 (2009).
-
182.
Trencsenyi, G., Kertai, P., Bako, F., Hunyadi, J., Marian, T., Hargitai, Z., Pocsi, I., Muranyi, E., Hornyak, L., Banfalvi, G.: Renal capsule-Parathymic lymph node complex: A new in vivo metastatic model in rats. Anticancer Res 29, 2121–2126 (2009).
-
183.
Trencsenyi, G., Juhasz, T., Bako, F., Marian, T., Pocsi, I., Kertai, K., Hunyadi, J., Banfalvi, G.: Comparison of the tumorigenic potential of liver and kidney tumors induced by N-nitrosodimethylamine. Histol Histopathol 25, 309–320 (2010).
-
184.
Banfalvi, G.: Metastatic view of breast cancer. Cancer Metast Rev 31, 815–822 (2012b).
-
185.
Choi, K., Kim, J., Kim, G. W., Choi, C.: Oxidative stress-induced necrotic cell death via mitochondira-dependent burst of reactive oxygen species. Curr Neurovasc Res 6, 213–222 (2009).
-
186.
Nagy, G., Hennig, G. W., Petrenyi, K., Kovacs, L., Pocsi, I., Dombradi, V., Banfalvi, G.: Time-lapse video microscopy and image analysis of adherence and growth patterns of Candida albicans strains. Appl Microbiol Biotechnol 98, 5185–5194 (2014).
-
187.
Shapira, A., Benhar, I.: Toxin-based therapeutic approaches. Toxins 2, 2519–2583 (2010).
-
188.
De Ruyck, K., De Boevre, M., Huybrechts, I., De Saeger, S.: Dietary mycotoxins, co-exposure, and carcinogenesis in humans: Short review. Mutat Res Rev Mutat Res 766, 32–41 (2015).
-
189.
Smith, M. C., Madec, S., Coton, E., Hymery, N.: Natural co-occurrence of mycotoxins in foods and feeds and their in vitro combined toxicological effects. Toxins (Basel) 8, 94 (2016).
-
190.
Azuma, H., Takahara, S., Ichimaru, N., Wang, J. D., Itoh, Y., Otsuki, Y., Morimoto, J., Fukui, R., Hoshiga, M., Ishihara, T., Nonomura, N., Suzuki, S., Okuyama, A., Katsuoka, Y.: Marked prevention of tumor growth and metastasis by a novel immunosuppressive agent, FTY720, in mouse breast cancer models. Cancer Res 62, 1410–1419 (2002).
