The Potential Role of Bone Marrow Derived Mesenchymal Stem Cells Conditioned Medium in the Suppression of Hepatocellular Carcinoma In Vitro: Modulation of Apoptosis
The Potential Role of Bone Marrow Derived Mesenchymal Stem Cells Conditioned Medium in the Suppression of Hepatocellular Carcinoma In Vitro: Modulation of Apoptosis
Mahmoud Abdelhady Metwally1*, Mona Abdelftah Ali1, Farouk Abdelmohdy1, Mohamed Kassab1, Tarek Kamal Abouzed2 and Khalil Fathy Abou-Easa1
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.
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