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Statistical optimization of environmental factors to produce the cytotoxic enniatins H, I and MK1688 against human multidrug resistance cancer cell lines

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Abstract

The environmental conditions were optimized to produce the enniatin H, I, and MK1688 by Fusarium strain on cereal grain exhibiting anti-carcinogenic potential against MES-SA (human uterine sarcoma cell line), HCT15 (human colorectal carcinoma cancer cell line), and their multidrug resistance sublines. From the statistical optimization by response surface methodology, the optimal condition of independent variables affecting the response variables were 20.85 °C (temperature), 46.85% (w/w, initial moisture content), and 18.42 days (growth time) for ENN H; 23.31 °C, 44.15% (w/w) and 17.23 days for ENN I; 23.08 °C, 43.97% (w/w) and 17.06 days for ENN MK1688. In case of cytotoxic effects, ENNs significantly suppressed growth of cancer cell lines without multidrug resistance, and ENN I inhibited growth of cancer cell lines most strongly. These data will provide valuable point to produce the cyclic hexadepsipeptide exhibiting anti-carcinogenic potential from Fusarium strains.

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References

  • Castella G, Bragulat MR, Cabañes FJ. Surveillance of fumonisins in maize-based feeds and cereals from Spain. Journal of Agricultural and Food Chemistry. 47(11): 4707-4710 (1999)

    Article  CAS  PubMed  Google Scholar 

  • Chauhan B, Gupta R. Application of statistical experimental design for optimization of alkaline protease production from Bacillus sp. RGR-14. Process Biochemistry. 39(12): 2115-2122 (2004)

    Article  CAS  Google Scholar 

  • Dornetshuber R, Heffeter P, Kamyar, MR, Peterbauer T, Berger W, Lemmens-Gruber R. Enniatin exerts p53-dependent cytostatic and p53-independent cytotoxic activities against human cancer cells. Chemical Research in Toxicology. 20: 465-473 (2007)

    Article  CAS  PubMed  Google Scholar 

  • Dornetshuber R, Heffeter P, Sulyok M, Schumacher R, Chiba P, Kopp S, Koellensperger G, Micksche M, Lemmens‐Gruber R, Berger W. Interactions between ABC‐transport proteins and the secondary Fusarium metabolites enniatin and beauvericin. Molecular nutrition & food research. 53: 904-920 (2009)

    Article  CAS  Google Scholar 

  • EFSA Panel on Contaminants in the Food Chain (CONTAM). Scientific Opinion on the risks to human and animal health related to the presence of beauvericin and enniatins in food and feed. EFSA Journal. 12: 3802 (2014)

    Article  Google Scholar 

  • Gupta S, Krasnoff SB, Underwood NL, Renwick J, Roberts DW. Isolation of beauvericin as an insect toxin from Fusarium semitectum and Fusarium moniliforme var. subglutinans. Mycopathologia. 115: 185-189 (1991).

    Article  CAS  PubMed  Google Scholar 

  • Hiraga K, Yamamoto S, Fukuda H, Hamanaka N, Oda K. Enniatin has a new function as an inhibitor of Pdr5p, one of the ABC transporters in Saccharomyces cerevisiae. Biochemical and biophysical research communications. 328: 1119-1125 (2005)

    Article  CAS  PubMed  Google Scholar 

  • Ivanova L, Skjerve E, Eriksen GS, Uhlig S. Cytotoxicity of enniatins A, A1, B, B1, B2 and B3 from Fusarium avenaceum. Toxicon. 47: 868-876 (2006)

    Article  CAS  PubMed  Google Scholar 

  • Kostecki M, Wisniewska H, Perrone G, Ritieni A, Jerzy PG, Chelkowski J, Logrieco A. The effects of cereal substrate and temperature on production of beauvericin, moniliformin and fusaproliferin by Fusarium subglutinans ITEM-1434. Food Additives & Contaminants. 16: 361-365 (1999)

    Article  CAS  Google Scholar 

  • Kriek N, Marasas W, Steyn P, Van Rensburg S, Steyn M. Toxicity of a moniliformin-producing strain of Fusarium moniliforme var. subglutinans isolated from maize. Food and Cosmetics Toxicology. 15: 579-587 (1977)

    Article  CAS  PubMed  Google Scholar 

  • Lee HS, Song HH, Jeong JH, Shin CG, Choi SU, Lee C. Cytotoxicities of enniatins H, I, and MK1688 from Fusarium oxysporum KFCC 11363P. Toxicon, 51: 1178-1185 (2008)

    Article  CAS  PubMed  Google Scholar 

  • Lee HS, Chanvorleak P, Nam WS, Lee C. Optimization of culture conditions of Fusarium solani for the production of neoN-methylsansalvamide. Bioscience, Biotechnology, and Biochemistry. 78: 1421-1427 (2014)

    Article  CAS  PubMed  Google Scholar 

  • Lee HS, Chanvorleak P, Choi SU, Lee C. Synergistic effect of a novel cyclic pentadepsipeptide, neoN-methylsansalvamide, and paclitaxel on human multidrug resistance cancer cell lines. Anti-Cancer Drug. 24: 455-460 (2014)

    Article  Google Scholar 

  • Luz C, Saladino F, Luciano F, Mañes J, Meca G. Occurrence, toxicity, bioaccessibility and mitigation strategies of beauvericin, a minor Fusarium mycotoxin. Food and Chemical Toxicology. 107: 430-439 (2017)

    Article  CAS  PubMed  Google Scholar 

  • Meca G, Sospedra I, Valero MA, Mañes J, Font G, Ruiz MJ. Antifungal effects of the bioactive compounds enniatins A, A1, B, B1. Toxicon. 56: 480-485 (2010)

    Article  CAS  PubMed  Google Scholar 

  • Meca G, Font G, Ruiz M. Comparative cytotoxicity study of enniatins A, A1, A2, B, B1, B4 and J3 on Caco-2 cells, Hep-G2 and HT-29. Food and Chemical Toxicology. 49: 2464-2469 (2011)

    Article  CAS  PubMed  Google Scholar 

  • Meca G, Sospedra I, Valero MA, Mañes J, Font G, Ruiz MJ. Antibacterial activity of the enniatin B, produced by Fusarium tricinctum in liquid culture, and cytotoxic effects on Caco-2 cells. Toxicology Mechanisms and Methods. 21: 503-512 (2011)

    Article  CAS  PubMed  Google Scholar 

  • Moretti P, Freeman K, Coodly L, Shore D. Evidence that a complex of SIR proteins interacts with the silencer and telomere-binding protein RAP1. Genes & development. 8(19): 2257-2269 (1994)

    Article  CAS  Google Scholar 

  • Nilanonta C, Isaka M, Chanphen R, Thong-orn N, Tanticharoen M, Thebtaranonth Y. Unusual enniatins produced by the insect pathogenic fungus Verticillium hemipterigenum: isolation and studies on precursor-directed biosynthesis. Tetrahedron. 59: 1015-1020 (2003)

    Article  CAS  Google Scholar 

  • Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, Warren JT, Bokesch H, Kenney S, Boyd MR. New colorimetric cytotoxicity assay for anticancer-drug screening. JNCI: Journal of the National Cancer Institute. 82(13): 1107-1112 (1990)

    Article  CAS  PubMed  Google Scholar 

  • Song HH, Lee HS, Lee GP, Ha SD, Lee C. Structural analysis of enniatin H, I, and MK1688 and beauvericin by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and their production by Fusarium oxysporum KFCC 11363P. Food Additives and Contaminants. 26: 518-526 (2009)

    Article  CAS  PubMed  Google Scholar 

  • Supothina S, Isaka M, Kirtikara K, Tanticharoen M, Thebtaranonth Y. Enniatin production by the entomopathogenic fungus Verticillium hemipterigenum BCC 1449. The Journal of Antibiotics. 57(11): 732-738 (2004)

    Article  CAS  PubMed  Google Scholar 

  • Tomoda H, Huang XH, Caoa J, Nishida H, Nagao R, Okuda S, Tanaka H, Omura S, Arai H, Inoque K. Inhibition of acyl-CoA: cholesterol acyltransferase activity by cyclodepsipeptide antibiotics. The Journal of Antibiotics. 45(10): 1626-1632 (1992)

    Article  CAS  PubMed  Google Scholar 

  • Tonshin AA, Teplova VV, Andersson MA, Salkinoja-Salonen MS. The Fusarium mycotoxins enniatins and beauvericin cause mitochondrial dysfunction by affecting the mitochondrial volume regulation, oxidative phosphorylation and ion homeostasis. Toxicology. 276(1): 49-57 (2010)

    Article  CAS  PubMed  Google Scholar 

  • Trenin A, Tolstykh I, Terekhova L, Zenkova V, Makarova M, Gladkikh E, Bychkova O, Katrujha G. The hypolipidemic action of antibiotic 86/88 (enniatin B) in a hepatoblastoma G2 cell culture. Antibiotiki i Khimioterapiia= Antibiotics and Chemoterapy [sic]. 45: 6-9 (2000)

    CAS  PubMed  Google Scholar 

  • Wätjen W, Debbab A, Hohlfeld A, Chovolou Y, Kampkötter A, Edrada RA, Ebel R, Hakiki A, Mosaddak M, Totzke F. 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. Molecular Nutrition & Food Research. 53: 431-440 (2009)

    Article  Google Scholar 

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Acknowledgements

This research was supported by his research was supported by a grant (21153MFDS605) from the Ministry of Food and Drug Safety, and the Chung-Ang University Graduate Research Scholarship (academic scholarship for College of Biotechnology and Natural Resources) in 2021.

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Correspondence to Hee-Seok Lee.

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Hwang, Y., Lee, HS. Statistical optimization of environmental factors to produce the cytotoxic enniatins H, I and MK1688 against human multidrug resistance cancer cell lines. Food Sci Biotechnol 33, 579–587 (2024). https://doi.org/10.1007/s10068-023-01363-5

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