Enhanced Anti-Cancer Effects of Conditioned Medium from Hypoxic Human Umbilical Cord–Derived Mesenchymal Stem Cells
- Author:
Kyu Hyun HAN
1
;
Ae Kyeong KIM
;
Gun Jae JEONG
;
Hye Ran JEON
;
Suk Ho BHANG
;
Dong Ik KIM
Author Information
- Publication Type:Original Article
- Keywords: Anti-cancer; Conditioned medium; Fibroblasts; Hypoxia; Mesenchymal stem cells
- MeSH: Activins; Anoxia; Apoptosis; Biological Processes; Cell Cycle; Cell Cycle Checkpoints; Cell Survival; Culture Media, Conditioned; Fibroblasts; Gene Ontology; Genome; HeLa Cells; Humans; Insulin-Like Growth Factor Binding Protein 3; Membrane Potential, Mitochondrial; Mesenchymal Stromal Cells; Tissue Inhibitor of Metalloproteinase-2; Uterine Cervical Neoplasms
- From:International Journal of Stem Cells 2019;12(2):291-303
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND AND OBJECTIVES: There have been contradictory reports on the pro-cancer or anti-cancer effects of mesenchymal stem cells. In this study, we investigated whether conditioned medium (CM) from hypoxic human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) (H-CM) showed enhanced anti-cancer effects compared with CM from normoxic hUC-MSCs (N-CM). METHODS AND RESULTS: Compared with N-CM, H-CM not only strongly reduced cell viability and increased apoptosis of human cervical cancer cells (HeLa cells), but also increased caspase-3/7 activity, decreased mitochondrial membrane potential (MMP), and induced cell cycle arrest. In contrast, cell viability, apoptosis, MMP, and cell cycle of human dermal fibroblast (hDFs) were not significantly changed by either CM whereas caspase-3/7 activity was decreased by H-CM. Protein antibody array showed that activin A, Beta IG-H3, TIMP-2, RET, and IGFBP-3 were upregulated in H-CM compared with N-CM. Intracellular proteins that were upregulated by H-CM in HeLa cells were represented by apoptosis and cell cycle arrest terms of biological processes of Gene Ontology (GO), and by cell cycle of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. In hDFs, negative regulation of apoptosis in biological process of GO and PI3K-Akt signaling pathway of KEGG pathways were represented. CONCLUSIONS: H-CM showed enhanced anti-cancer effects on HeLa cells but did not influence cell viability or apoptosis of hDFs and these different effects were supported by profiling of secretory proteins in both kinds of CM and intracellular signaling of HeLa cells and hDFs.
