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

Abstract

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 µg/ml) for 48-72 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 2-6% and 30-60%, while Transwell migration assay showed inhibition by 20-26% and 31-46% 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.

Human Umbilical Cord Mesenchymal Stem Cells: A New Era for Stem Cell Therapy

“…HUCMSCs also decrease the xenograft tumor size, and the phosphoinositide-3-kinase (PI3K) and Akt signaling pathways play roles in this anticancer effect. Another study has used MDA-231 and TOV-112D cells (latter is from an endometrioid carcinoma of a 42-year-old female) as a tumor formation model (23). Conditioned medium and cell lysates of HUCMSCs have been used for treating cancer cell lines.…”

The Effect of Wharton's Jelly Mesenchymal Stem Cells on a Squamous Cell Carcinoma Cell Line

“…Moreover, WJMSC-conditioned medium was used for treating the HEP-2 cell line rather than cell co-culturing, which is sometimes unreliable owing to the likelihood of one cell type showing increased growth than the other caused by the culture medium instead of a true anticancer effect [26]. To exclude this possibility, the present study focused on the role of WJMSCconditioned medium rather than the cell itself.…”

“…Gauthman et al, [26] examined the effect of umbilical cord WJMSC extract on three cancer cell lines: breast adenocarcinoma, ovarian carcinoma, and osteosarcoma. They found that the three cancer cell lines showed different levels of anticancer activity; the effects were most severe on osteosarcoma and least on ovarian carcinoma.…”

“…According to a recent report [25], human umbilical cord MSCs inhibited the growth of breast cancer cells in a severe combined immunodeficiency (SCID) mouse model by secreting dickkopf and suppressing the WNT signaling pathway. In a more recent report, Gauthaman et al, [26] examined the effect of WJMSC extracts (conditioned medium) on three cancer cell lines: breast adenocarcinoma (MDA-MB-231), ovarian carcinoma (TOV-112D), and osteosarcoma (MG-63). They found that all three cancer cell lines exhibited cell shrinkage, blebbing, and vacuolation suggestive of apoptosis.…”

“…These include induction of transcriptional activity, distinctive expression of functional genes, and reprogramming of distinct cell types [31]. Nevertheless, the molecules in the extracts that are assumed to cause cell changes have not been identified [26].…”