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

• Published in: Molecular biology reports Vol. 51; no. 1; p. 740
• Main Authors: Abdel-Tawab, Marwa Sayed, Fouad, Hanan, Sedeak, Ahmed Yahia, Doudar, Noha A., Rateb, Enas Ezzat, Faruk, Eman, Reyad, Hoda Ramadan
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.12.2024; Springer Nature B.V
• Subjects: Animal Anatomy; Animal Biochemistry; Animals; Biomedical and Life Sciences; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell differentiation; Curcumin; Curcumin - pharmacology; Disease Models, Animal; Down-regulation; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Gene regulation; Hedgehog protein; Hedgehog Proteins - genetics; Hedgehog Proteins - metabolism; Hepatocellular carcinoma; Histology; Homeostasis; Life Sciences; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal stem cells; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - metabolism; Morphology; Original Article; Patched-1 Receptor - genetics; Patched-1 Receptor - metabolism; Pathology; Rats; Signal transduction; Signal Transduction - drug effects; Stem cells; Zinc Finger Protein GLI1 - genetics; Zinc Finger Protein GLI1 - metabolism; Sonic hedgehog; HCC; MSCs; Curcumin; SHH; And GLI1; SMOH; PTCH1
• ISSN: 0301-4851; 1573-4978; 1573-4978
• DOI: 10.1007/s11033-024-09613-3

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.