The Potential Role of Bone Marrow Derived Mesenchymal Stem Cells Conditioned Medium in the Suppression of Hepatocellular Carcinoma In Vitro: Modulation of Apoptosis | [Pakistan Journal of Zoology • 2023]

Author(s):

1. Mahmoud Abdelhady Metwally: Department of Cytology and Histology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt

2. Mona Abdelftah Ali: Department of Cytology and Histology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt

3. Farouk Abdelmohdy: Department of Cytology and Histology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt

4. Mohamed Kassab: Department of Cytology and Histology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt

5. Tarek Kamal Abouzed: Department of Biochemistry, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt.

6. Khalil Fathy Abou-Easa: Department of Cytology and Histology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt

Abstract:

Bone marrow mesenchymal stem cells (BMMSCs) can home to cancerous cells and suppress their growth. However, few studies have investigated the impact of conditioned medium harvested from BMMSCs on carcinogenesis. This study investigated the effect of BMMSCs-conditioned medium (BMMSCs-CM) on the hepatoma cell line HepG2 and described the underlying molecular mechanisms involved. We isolated BMMSCs and identified them using flowcytometry and culture characteristics, then prepared BMMSCs-CM. HepG2 cells were treated with various concentrations of BMMSCs-CM for up to 72 h. The methylthiazolyldiphenyl-tetrazolium (MTT) assay showed decreased proliferation, while flowcytometry showed increased apoptosis and cell cycle arrest in the G0/G1 phase with inhibition of entry into the S phase. RT-PCR showed p53 upregulation and Bcl-2 downregulation in mRNA expression. Moreover, Western blotting and flowcytometry revealed elevated p53 and lowered Bcl-2 protein levels. In addition, ELISA findings showed decreased toll-like receptor 4 (TLR4) concentration. Taken together, our findings highlight the potent therapeutic function of BMMSCs-CM in suppressing HepG2 cancerous cells across multiple platforms, including proliferation, apoptosis, cell cycle, and oncogene expression. Furthermore, our findings suggest that the Notch and TLR4/NF-kB signaling pathways may be targets of BMMSCs-CM for tumor cell suppression.

Page(s): 2595-2606

DOI: 10.17582/journal.pjz/20220316180305

Published: Journal: Pakistan Journal of Zoology, Volume: 55, Issue: 6, Year: 2023

Keywords:

Liver Cancer , Hepatocellular carcinoma , Bone marrowderived Mesenchymal stem cells , HepG2 cell apoptosis , Mesenchymal stem cells conditioned medium

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