4.6 Article

Human umbilical cord wharton's jelly stem cell (hWJSC) extracts inhibit cancer cell growth in vitro

Journal

JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 113, Issue 6, Pages 2027-2039

Publisher

WILEY
DOI: 10.1002/jcb.24073

Keywords

APOPTOSIS; AUTOPHAGY; CANCER CELLS; CELL INHIBITION; HUMAN WHARTON'S JELLY STEM CELL CONDITIONED MEDIUM AND LYSATE

Funding

  1. National Medical Research Council (NMRC), Singapore [R-174-000-131-213]

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Umbilical cord mesenchymal stem cells (MSCs) have been shown to inhibit breast cancer cell growth but it is not known whether this effect is specific to only breast cancer cells. We compared the effects of human Wharton's jelly stem cell (hWJSC) extracts [conditioned medium (hWJSC-CM) and cell lysate (hWJSC-CL)] on breast adenocarcinoma (MDA-MB-231), ovarian carcinoma (TOV-112D), and osteosarcoma (MG-63) cells. The cells were treated with either hWJSC-CM (50%) or hWJSC-CL (15 mu g/ml) for 4872?h and changes in cell morphology, proliferation, cycle, gene expression, migration, and cell death studied. All three cancer cell lines showed cell shrinkage, blebbing, and vacuolations with hWJSC-CL and hWJSC-CM compared to controls. MTT and BrdU assays showed inhibition of cell growth by 26% and 3060%, while Transwell migration assay showed inhibition by 2026% and 3146% for hWJSC-CM and hWJSC-CL, respectively, for all three cancer cell lines. Cell cycle assays showed increases in sub-G1 and G2/M phases for all three cancer cell lines suggestive of apoptosis and metaphase arrest. AnnexinV-FITC and TUNEL positive cells seen in TOV-112D and MDA-MB-231 suggested that inhibition was via apoptosis while the presence of anti-BECLIN1 and anti-LC3B antibodies seen with MG-63 indicated autophagy. Upregulation of pro-apoptotic BAX and downregulation of anti-apoptotic BCL2 and SURVIVIN genes were observed in all three cancer cell lines and additionally the autophagy genes (ATG5, ATG7, and BECLIN1) were upregulated in MG-63 cells. hWJSCs possess tumor inhibitory properties that are not specific to breast cancer cells alone and these effects are mediated via agents in its extracts. J. Cell. Biochem. 113: 20272039, 2012. (C) 2012 Wiley Periodicals, Inc.

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