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

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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.

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Acknowledgements

Authors extend their appreciation to the International Center for training and Advanced Researches (ICTAR–Egypt) for partial financial supporting this work through research groups. Also, the authors extend their appreciation to Al-Azhar University.

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Authors and Affiliations

  1. The International center for training and advanced researches (ICTAR –Egypt), Cairo, Egypt

    Aly Fahmy Mohamed

  2. Histology department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt

    Tamer M. M. Abuamara

  3. Histology department, Faculty of medicine, Al-Azhar University, Damietta, Egypt

    Mohamed E. Amer & Tamer Albasyoni Gomah

  4. Histology department, Faculty of medicine (girls), Al-Azhar University, Damietta, Egypt

    Laila E. EI-Moselhy

  5. Pathology Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt

    Emadeldin R. Matar

  6. Microbiology and Immunology Department, Faculty of Pharmacy, Ahram Canadian University, Cairo, Egypt

    Rania Ibrahim Shebl

  7. Department of Botany and Microbiology, Faculty of Science, Al-Azhar Uniersity, 11847, Nasr City, Cairo, Egypt

    Said E. Desouky & Mohammed Abu-Elghait

Authors
  1. Aly Fahmy Mohamed
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  2. Tamer M. M. Abuamara
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  3. Mohamed E. Amer
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  8. Said E. Desouky
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  9. Mohammed Abu-Elghait
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Contributions

Aly Fahmy Mohamed: conceptualization, methodology, resources, investigation, software, writing-original draft. Tamer. M. M. Abuamara: resources, investigation, software, writing-review. Mohamed E. Amer: methodology, investigation, software, writing-review. Laila. E. EI-Moselhy: methodology, resources, validation, writing-review. Tamer Albasyoni Gomah: methodology, software, validation, writing-review Said Desouky: methodology, investigation, software, validation, writing-review. Emadeldin R. Matar: methodology, resources, software, validation, writing-review. Rania Ibrahim Shebl: methodology, resources, investigation, writing-original draft, writing-review. Mohammed Abu-Elghait: conceptualization, methodology, resources, investigation, software, writing-original draft, writing-review, editing and submitting the paper to the journal.

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Correspondence to Mohammed Abu-Elghait.

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Key Points

• Aspergillus terreus, Aspergillus flavus, and Aspergillus fumigatus secondary metabolite induce toxic effect against Human colonic adenocarcinoma cells (Caco-2) and Hepatocyte derived cellular carcinoma cells (HuH-7).

• Up regulation of pro-apoptotic genes and down-regulation of anti-apoptotic genes was detected. The expression level was cell type dependent.

• Aspergillus secondary metabolites are promising agents that can be used as supplementary agents to currently applied anti- cancer drug regimen.

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Mohamed, A.F., Abuamara, T.M.M., Amer, M.E. et al. Genetic and Histopathological Alterations in Caco-2 and HuH-7 Cells Treated with Secondary Metabolites of Marine fungi. J Gastrointest Canc 53, 480–495 (2022). https://doi.org/10.1007/s12029-021-00640-y

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