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Effects of mesenchymal stem cells versus curcumin on sonic hedgehog signaling in experimental model of Hepatocellular Carcinoma

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Abstract

Background

Sonic Hedgehog (SHH) is a fundamental signaling pathway that controls tissue reconstruction, stem cell biology, and differentiation and has a role in gut tissue homeostasis and development. Dysregulation of SHH leads to the development of HCC.

Methods, and results

The present study was conducted to compare the effects of mesenchymal stem cells (MSCs) and curcumin on SHH molecular targets in an experimental model of HCC in rats. One hundred rats were divided equally into the following groups: control group, HCC group, HCC group received MSCs, HCC group received curcumin, and HCC group received MSCs and curcumin. Histopathological examinations were performed, and gene expression of SHH signaling target genes (SHH, PTCH1, SMOH, and GLI1) was assessed by real-time PCR in rat liver tissue. Results showed that SHH target genes were significantly upregulated in HCC-untreated rat groups and in MSC-treated groups, with no significant difference between them. Administration of curcumin with or without combined administration of MSCs led to a significant down-regulation of SHH target genes, with no significant differences between both groups. As regards the histopathological examination of liver tissues, both curcumin and MSCs, either through separate use or their combined use, led to a significant restoration of normal liver pathology.

Conclusions

In conclusion, SHH signaling is upregulated in the HCC experimental model. MSCs do not inhibit the upregulated SHH target genes in HCC. Curcumin use with or without MSCs administration led to a significant down-regulation of SHH signaling in HCC and a significant restoration of normal liver pathology.

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Data availability

No datasets were generated or analysed during the current study.

Abbreviations

HCC:

Hepatocellular carcinoma

MSCs:

Mesenchymal stem cells

SHH:

Sonic Hedgehog

PTCH1:

Patched 1

SMOH:

Smoothened homolog

GLI1:

Glioma-associated oncogene

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Acknowledgements

The researchers are grateful for all the medical experts who helped with the research process.

Funding

This research received no specific funding from any governmental funding agency.

Author information

Authors and Affiliations

  1. Medical Biochemistry Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt

    Marwa Sayed Abdel-Tawab & Hoda Ramadan Reyad

  2. Medical Biochemistry Department, Faculty of Medicine, Cairo University, POB 12613, Cairo, Egypt

    Hanan Fouad

  3. Faculty of Medicine, Galala University, POB 43711, Attaka, Suez Governorate, Egypt

    Hanan Fouad

  4. Clinical and Chemical Pathology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt

    Noha A. Doudar

  5. Physiology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt

    Enas Ezzat Rateb

  6. Department of Anatomy, Faculty of Medicine, Umm Al-Qura University, Mecca, Saudi Arabia

    Eman Faruk

  7. Department of Histology and Cytology, Faculty of Medicine, Benha University, Benha, Egypt

    Eman Faruk

  8. Anatomy and Embryology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt

    Ahmed Yahia Sedeak

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  1. Marwa Sayed Abdel-Tawab
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Contributions

The study’s architecture, analysis of data, and article writing were significantly aided by MA. ER performed experimental animal work. HR, and ND finishing up the molecular work and analysis. HF, EF, and MA analyzed the clinical data. AY and EF carried out the histological examination and analysis. Moreover, HF and AY carried out statistical analysis. All writers reviewed and approved the final version of the work in addition to doing the final manuscript review.

Corresponding author

Correspondence to Marwa Sayed Abdel-Tawab.

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Ethical approval

In compliance with National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) guidelines, the Institutional Animal Care and Use Committee of Beni-Suef University (BSU-IACUC) approved the current study’s protocol with the code 022–454.

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There were no specifics, pictures, or videos in our raw data or manuscript.

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The writers declared that they had no possible conflicts of interest about the research, writing, or publication of this work.

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Abdel-Tawab, M.S., Fouad, H., Sedeak, A.Y. et al. Effects of mesenchymal stem cells versus curcumin on sonic hedgehog signaling in experimental model of Hepatocellular Carcinoma. Mol Biol Rep 51, 740 (2024). https://doi.org/10.1007/s11033-024-09613-3

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