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In vivo Study of a Newly Synthesized Chromen-4-one Derivative as an Antitumor Agent against HCC

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Abstract

Background

Chromenes are a wide group of natural compounds that can be synthesized chemically. The chromen-4-one nucleus acts as a skeleton for varieties of additional active groups that makes the chromene activity vary between antioxidant and anti-inflammatory agents. In the present study, a newly synthesized chromene compound exhibits different behaviors other than anti-inflammatory and antioxidant activities that it is the first time that a member of chromen-4-one compound can control the cancer progress. Inflammation is the first step in tumor development where the severity grade can potentiate tumor growth and progression. In many tumors, pro-inflammatory genes record high expression level such as tumor necrosis factor (TNF-α) and vascular endothelial growth factors (VEGF). These pro-inflammatory factors act as rate limiting steps in tumor initiation, and controlling its expression acts as an early therapeutic way to control the tumor proliferation. The chromone derivatives have biological activities such as anti-inflammatory and anti-tumor activity.

Methods

In the present study, hepatocellular cancer (HCC) induced by diethylnitrosamine (DEN) in rats and then treated with the new chromene derivative and the parameters TNF-α, VEGF, p53, Cyt C, MMP-9, Bcl2, and Bax were measured.

Results

The treatment strategy Ch compound is to downregulate pro-inflammatory gene expression of early genes as TNF-α as well as VEGF and subsequently control other factors such as p53, Cyt C, and MMP-9. Also, retrieve the balance between Bcl2 and Bax proteins in DEN-induced HCC in rats.

Conclusion

The ability of the new Ch derivative to control the primary initiators of HCC such as TNF-α offers this derivative an anti-tumor activity and encourages further researches to follow and monitor its effect on the molecular level.

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Abbreviations

TNF-α:

Tumor necrosis factor alpha

VEGF:

Vascular endothelial growth factors

HCC:

Hepatocellular cancer

DCO-6:

(E)-5,7-dihydroxy-3-(3-oxo-3-phenylprop-1-en-1-yl)-4H-chromen-4-one

NO:

Nitric oxide

EAC:

Ehrlich ascites carcinoma

HCV:

Hepatitis C virus

MDA:

Malonaldehyde

ROS:

Reactive oxygen species

MMP:

Metalloproteinase

Cyt c:

Cytochrome C

NCRRT:

National Center for Radiation Research & Technology

DEN:

Diethylnitrosamine

Ch:

[(2E)-2-(4-oxo-4H-chromen-3-yl)methylene amino-4-nitrobenzoic acid

IACUC:

Institutional Animal Care and Use Committee

ALT:

L-alanine aminotransferase

AST:

Aspartate amino transferase

ELISA:

Enzyme-linked immunosorbent assay

AFP:

Alpha-fetoprotein

RT-PCR:

Real-time polymerase chain reaction

cDNA:

Cloned deoxyribonucleic acid

RNA:

Ribonucleic acid

qPCR:

Quantitative real-time polymerase chain reaction

LSD:

Least significant difference

SPSS:

Statistical Package for Social Science

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Acknowledgements

We appreciate the management of Egyptian Atomic Energy Authority for facilities provided to build up this work.

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Authors and Affiliations

  1. Biochemistry Lab Chemistry Department Faculty of Education, Ain Shams University, Cairo, Egypt

    Asmaa I. Nabeel

  2. Department of Radiation Biology, National Center of Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt

    Somaya Z. Mansour

  3. Department of Chemistry, Faculty of Science, Helwan University, Cairo, Egypt

    Hatem A. El-Mezayen

  4. Chemistry Administration, Cairo, Egypt

    Sarah A. Mohamed

Authors
  1. Asmaa I. Nabeel
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  2. Somaya Z. Mansour
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  3. El-Sayed M. E. Mahdy
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  4. Hatem A. El-Mezayen
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  5. Sarah A. Mohamed
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Contributions

All authors have read and approved the manuscript. A. I. Nabeel donated the chromen-4-one new derivative and wrote the manuscript. S. Z. Mansourshared the laboratory and animal house for work. E. M. E. Mahdycontributed the idea and plan of work. H. A. El-Mezayen revision role. S. A. Mohamedapply the practical work and share the writing of manuscript.

Corresponding author

Correspondence to Asmaa I. Nabeel.

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Animal dealing conditions and treatment were guided as per the National Institute of Health Guide for Animal and approved by the Institutional Animal Care and Use Committee (IACUC). Reference: National Research Council (US) Committee for the Update of the Guide. Guide for the care and use of laboratory animals. 8th ed. Washington, DC: National Academies Press, 2011.

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Summary

• Chromones are effective compounds as anti-inflammatory agents, and some researches pointed out the anti-tumor activity of chromones in vitro.

• The Ch compound is one of chromone derivatives, and we studied its anti-tumor activity in vivo. HCC was induced in rats DEN and treated with Ch compound.

• The treatment with Ch compound rebalances the biochemical markers to shift the body status away from HCC disturbance to the normal balance through blocking of TNF-α.

• Ch compound could be an effective agent for controlling the tumor status.

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Nabeel, A.I., Mansour, S.Z., Mahdy, ES.M.E. et al. In vivo Study of a Newly Synthesized Chromen-4-one Derivative as an Antitumor Agent against HCC. J Gastrointest Canc 53, 980–989 (2022). https://doi.org/10.1007/s12029-021-00724-9

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  • DOI: https://doi.org/10.1007/s12029-021-00724-9

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