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Journal of Gastrointestinal Cancer
Published in: Journal of Gastrointestinal Cancer 2/2022

11-05-2021 | Original Research

Genetic and Histopathological Alterations in Caco-2 and HuH-7 Cells Treated with Secondary Metabolites of Marine fungi

Authors: Aly Fahmy Mohamed, Tamer M. M. Abuamara, Mohamed E. Amer, Laila E. EI-Moselhy, Tamer Albasyoni Gomah, Emadeldin R. Matar, Rania Ibrahim Shebl, Said E. Desouky, Mohammed Abu-Elghait

Published in: Journal of Gastrointestinal Cancer | Issue 2/2022

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Abstract

The present work aimed to study the activity of naturally derived fungal secondary metabolites as anticancer agents concerning their cytotoxicity, apoptotic, genetic, and histopathological profile. It was noticed that Aspergillus terreus, Aspergillus flavus, and Aspergillus fumigatus induced variable toxic potential that was cell type, secondary metabolite type, and concentration dependent. Human colonic adenocarcinoma cells (Caco-2) showed less sensitivity than hepatocyte-derived cellular carcinoma cells (HuH-7), and in turn, the half-maximal inhibitory concentration (IC50) was variable. Also, the apoptotic potential of Aspergillus species-derived fungal secondary metabolites was proven via detection of up-regulated pro-apoptotic genes and down-regulation of anti-apoptotic genes. The expression level was cell type dependent. Concurrently, apoptotic profile was accompanied with cellular DNA accumulation at the G2/M phase, as well as an elevation in Pre-G1 phase but not during G0/G1 and S phases. Also, there were characteristic apoptotic features of treated cells presented as abnormal intra-nuclear eosinophilic structures, dead cells with mixed euchromatin and heterochromatin, ruptured cell membranes, apoptotic cells with irregular cellular and nuclear membranes, as well as peripheral chromatin condensation. It can be concluded that Aspergillus secondary metabolites are promising agents that can be used as supplementary agents to the currently applied anti-cancer drug regimen.
Literature
1.
Cragg GM, Newman DJ. Nature a vital source of leads for anticancer drug development. Phytochem Rev. 2009;2009(8):313–31.CrossRef
2.
Cragg GM, Grothaus PG, Newman DJ. Impact of natural products on developing new anticancer agents. Chem Rev. 2009;109:3012–43.PubMedCrossRef
3.
Newman DJ, Cragg GM. Natural products as sources of new drugs over the last 25 Years. J Nat Prod. 2007;70:461–77.PubMedCrossRef
4.
Lima RT, Guimarães JE, Vasconcelos MH Overcoming K562Dox resistance to STI571 (Gleevec) by down regulation of P-gp expression using siRNAs. Cancer Ther. 5:67–76.
5.
Newman DJ, Cragg GM. Marine natural products and related compounds in clinical and advanced preclinical trials. J Nat Prod. 2004;67:1216–38.PubMedCrossRef
6.
Simmons TL, Andrianasolo E, McPhail K, Flatt PM, Gerwick WH. Marine natural products as anticancer drugs. Mol Cancer Ther. 2005;4:333–42.PubMed
7.
Simmons TL, Coates RC, Clark BR, Eugene N, Gonzalez D, Esquenazi E, et al. Biosynthetic origin of natural products isolated from marine organisms-invertebrate assemblages. Proc Natl Acad Sci USA. 2008;105:4587–94.PubMedPubMedCentralCrossRef
8.
Bugni TS, Ireland CM. Marine-derived fungi: a chemically and biologically diverse group of microorganisms. Nat Prod Rep. 2004;21:143–64.PubMedCrossRef
9.
Podojil M, Sedmera P, Vokoun J, Betina V, Baráthová H, Ďuračková C, et al. Eurotium (Aspergilus) repens metabolites and their biological activity. Folia Microbiol. 1979;23:438–43.CrossRef
10.
Smetanina OF, Kalinovskii AI, Khudyakova YV, Slinkina NN, Pivkin MV, Kuznetsova TA. Metabolites from the marine fungus Eurotium repens. Chem Nat Comp. 2007;43:395–8.CrossRef
11.
Li X-D, Li X, Li XM, Xu GM, Zhang P, Meng LH, et al. Tetranorlabdane diterpenoids from the deep sea sediment derived fungus Aspergillus wentii SD-310. Planta Med. 2016;82:877–81.PubMedCrossRef
12.
Slack GJ, Puniani E, Frisvad JC, Samson RA, Miller JD. Secondary metabolites from Eurotium species, Aspergillus calidoustus and A. insuetus common in Canadian homes with a review of their chemistry and biological activities. Mycol Res. 2009;113:480–90.PubMedCrossRef
13.
Visalakchi S, Muthumary J. (2010): Taxol (anticancer drug) producing endophytic fungi: an overview. Int J Pharm Bio Sci. 2010;1:1–9.
14.
Li JE, Cui SW, Nie SP, Xie MY. Structure and biological activities of a pectic polysaccharide from Mosla chinensis Maxim. cv Jiangxiangru. Carbohyd Polym. 2014;105:276–84.CrossRef
15.
Grove JF. The structure of Terrein. J Chem Soc. 1954;4693–4.
16.
Dunn AW, Ian DE, Johnstone AW. Terrein and other metabolites of Phoma species. Phytochemistry. 1975;14:2081–2.CrossRef
17.
18.
Park SH, Kim DS, Kim WG, Ryoo IJ, Lee DH, Huh CH, et al. Terrein: a new melanogenesis inhibitor and its mechanism. Cell Mol Life Sci. 2004;61:2878–85.PubMedCrossRef
19.
20.
Lee HY, Jung JE, Kim JS, Lee HN, Yi KH. Terrein reduces age-related inflammation induced by oxidative stress through Nrf2/ERK1/2/HO-1 signalling in aged HDF cells. Cell Biochem Funct. 2015;33:479–86.PubMedCrossRef
21.
Liao WY, Shen CN, Lin LH, Yang YL, Han HY. Asperjinone, a nor-neolignan, and terrein, a suppressor of ABCG2-expressing breast cancer cells, from thermophilic Aspergillus terreus. J Nat Prod. 2012;75:630–5.PubMedCrossRef
22.
Arakawa M, Someno T, Kawada M, Ikeda D. A new terrein glucoside, a novel inhibitor of angiogenin secretion in tumor angiogenesis. J Antibiot. 2008;61:442–8.CrossRef
23.
Liao W-Y, Shen C-N, Lin L-H, Yang Y-L, Han H-Y, Chen J-W, Kuo S-C, Wu S-H, Liaw CC. Asperjinone, a nor-neolignan, and terrein, a suppressor of ABCG2-expressing breast cancer cells, from thermophilic Aspergillus terreus. J Nat Prod. 2012;75:630–5.PubMedCrossRef
24.
Rebacz B, Larsen TO, Clausen MH, Rønnest MH, Löffler H, Ho AD, Krämer A. Identification of griseofulvin as an inhibitor of centrosomal clustering in a phenotype-based screen. Cancer Res. 2007;67:6342–50.PubMedCrossRef
25.
Rønnest MH, Rebacz B, Markworth L, Terp AH, Larsen TO, Krämer A, Clausen MH. Synthesis and structure-activity relationship of griseofulvin analogues as inhibitors of centrosomal clustering in cancer cells. J Med Chem. 2009;52:3342–7.PubMedCrossRef
26.
Muroga Y, Yamada T, Numata A, Tanaka R. 11- and 4’-epimers of chaetomugilin A, novel cytostatic metabolites from marine fish-derived fungus Chaetomium globosum. Helv Chim Acta. 2010;93:542–9.CrossRef
27.
Panda D, Rathinasamy K, Santra MK, Wilson L. Kinetic suppression of microtubule dynamic instability by griseofulvin: implications for its possible use in the treatment of cancer. Proc Natl Acad Sci USA. 2005;102:9878–83.PubMedPubMedCentralCrossRef
28.
Yamada T, Jinno M, Kikuchi T, Kajimoto T, Numata A, Tanaka R. Three new azaphilones produced by a marine fish-derived Chaetomium globosum. J Antibiot. 2012;65:413–7.CrossRef
29.
30.
Kim SH, Lee SC, Song YS. Involvement of both extrinsic and Intrinsic apoptotic pathways in apoptosis induced by genistein in human cervical cancer cells. Ann NY Acad Sci. 2009;1171:196–201.PubMedCrossRef
31.
Hougardy BM, van der Zee AG, van den Heuvel FA, Timmer T, de Vries EG, de Jong S. Sensitivity to Fas-mediated apoptosis in high-risk HPV- positive human cervical cancer cells: relationship with Fas, caspase-8, and Bid. Gynecol Oncol. 2005;97:353–64.PubMedCrossRef
32.
Schiff PB, Fant J, Horwitz SB. Promotion of microtubule assembly in vitro by taxol. Nature. 1979;277:665–7.PubMedCrossRef
33.
Chen G-D, Li Y-J, Gao H, Chen Y, Li X-X, Li J, Guo L-D, Cen Y-Z, Yao X-S. New azaphilones and chlorinated phenolic glycosides from Chaetomium elatum with caspase-3 inhibitory activity. Planta Med. 2012;78:1683–9.PubMedCrossRef
34.
Ahn J-W, Lee M-K, Choi S-U, Lee C-O, Kim B-S. Cytotoxic ophiobolins produced by Bipolaris sp. J Microbiol Biotechn. 1998;8:406–8.
35.
Singh SB, Smith JL, Sabnis GS, Dombrowski AW, Schaeffer JM, Goetz MA, Bills GF. Structure and conformation of ophiobolin K and 6- epiophiobolin K from Aspergillus ustus as a nematocidal agent. Tetrahedron. 1991;47:6931–8.CrossRef
36.
Nozoe S, Itai A, Tsuda K, Okuda S. The chemical transformation of cephalonic acid. Tetrahedron Lett. 1967;42:4113–7.PubMedCrossRef
37.
Bills GF, Platas G, Gams W. Conspecificity of the cerulenin and helvolic acid producing “Cephalosporium caerulens”, and the hypocrealean fungus Sarocladium oryzae. Mycol Res. 2004;108:1291–300.PubMedCrossRef
38.
Pardo J, Urban C, Galvez EM, Ekert PG, Müller U, Kwon-Chung J, Lobigs M, Müllbacher A, Wallich R, Borner C, Simon MM. The mitochondrial protein Bak is pivotal for gliotoxin-induced apoptosis and a critical host factor of Aspergillus fumigatus virulence in mice. JCB Home » Archive. 2016;174 (4): 509.
39.
Li H, Liu X, Xu Y, Wang X, Zhu H. Structure and antitumor activity of the extracellular polysaccharides from Aspergillus aculeatus via apoptosis and cell cycle arrest. Glycoconj J. 2016;33:975-984.
40.
41.
Waring P, Beaver J. Gliotoxin and related Epipolythio dioxopiperazines. Gen Pharmacol. 1996;27:1311–6.PubMedCrossRef
42.
Gardiner DM, Waring P, Howlett BJ. The epipolythio dioxopiperazine (ETP) class of fungal toxins: distribution, mode of action, functions and biosynthesis. Microbiology. 2005;151:1021–32.PubMedCrossRef
43.
Pardo J, Urban C, Galvez EM, et al. The mitochondrial protein Bak is pivotal for gliotoxin-induced apoptosis and a critical host factor of Aspergillus fumigatus virulence in mice. J Cell Biol. 2006;174:509–19.PubMedPubMedCentralCrossRef
44.
Hamed A, Abdel-Razek AS, Araby M, Abu-Elghait M, El-Hosari DG, Frese M, Shaaban M. Meleagrin from marine fungus Emericella dentata Nq45: crystal structure and diverse biological activity studies. Nat Prod Res. 2020;1–9.
45.
Mohamed AA, Abu-Elghait M, Ahmed NE, Salem SS. Eco-friendly Mycogenic Synthesis of ZnO and CuO Nanoparticles for In Vitro Antibacterial, Antibiofilm, and Antifungal Applications. Biol Trace Elem Res. 2020:1–12.
46.
Abu-Elghait M, Hasanin M, Hashem AH, Salem SS. Ecofriendly novel synthesis of tertiary composite based on cellulose and myco-synthesized selenium nanoparticles: Characterization, antibiofilm and biocompatibility. Int J Biol Macromol. 2021;175:294–303.PubMedCrossRef
47.
Salem SS, Mohamed A, El-Gamal M, Talat M, Fouda A. Biological decolorization and degradation of azo dyes from textile wastewater effluent by Aspergillus niger. Egypt J Chem. 2019;62(10):1799–813.
48.
Hashem AH, Khalil AMA, Reyad AM, Salem SS. Biomedical applications of mycosynthesized selenium nanoparticles using Penicillium expansum ATTC 36200. Biol Trace Elem Res. 2021;1–11.
49.
Salem SS, Fouda MM, Fouda A, Awad MA, Al-Olayan EM, Allam AA, Shaheen TI. Antibacterial, cytotoxicity and larvicidal activity of green synthesized selenium nanoparticles using Penicillium corylophilum. J Cluster Sci. 2021;32(2):351–61.CrossRef
50.
Abdelmoneim HE, Wassel MA, Elfeky AS, Bendary SH, Awad MA, Salem SS, Mahmoud SA. Multiple applications of CdS/TiO 2 nanocomposites synthesized via microwave-assisted sol–gel. J Clust Sci. 2021;1–10.
51.
Desouky SE, Hassan SE, El-gamal MS, Ragab MAETI, Emam M. Effect of Salvia egypticae and Foeniculum vulgara extracts on quorum sensing and biofilm formation of methicillin resistant/sensitive staphylococcus aureus isolates. World J Pharm Med Res. 2017;3:466–75.
52.
Abdelhameed RM, Abu-Elghait M, El-Shahat M. Hybrid three MOFs composites (ZIF-67@ ZIF-8@ MIL-125-NH2): enhancement the biological and visible-light photocatalytic activity. J Environ Chem Eng. 2020;8(5):104107.CrossRef
Metadata
Title
Genetic and Histopathological Alterations in Caco-2 and HuH-7 Cells Treated with Secondary Metabolites of Marine fungi
Authors
Aly Fahmy Mohamed
Tamer M. M. Abuamara
Mohamed E. Amer
Laila E. EI-Moselhy
Tamer Albasyoni Gomah
Emadeldin R. Matar
Rania Ibrahim Shebl
Said E. Desouky
Mohammed Abu-Elghait
Publication date
11-05-2021
Publisher
Springer US
Published in
Journal of Gastrointestinal Cancer / Issue 2/2022
Print ISSN: 1941-6628
Electronic ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-021-00640-y

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