title: 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.
authors.affiliation: Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore.
authors.forename: Kalamegam
authors.initials: K
authors.lastname: Gauthaman
authors.forename: Fong Chui
authors.initials: FC
authors.lastname: Yee
authors.forename: Suganya
authors.initials: S
authors.lastname: Cheyyatraivendran
authors.forename: Arijit
authors.initials: A
authors.lastname: Biswas
authors.forename: Mahesh
authors.initials: M
authors.lastname: Choolani
authors.forename: Ariff
authors.initials: A
authors.lastname: Bongso
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000276:immunology; D000071187:Autophagy-Related Protein 5; D000071193:Autophagy-Related Protein 7; D000071186:Beclin-1; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002457:Cell Extracts / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis; D008565:Membrane Proteins / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000077022:Survivin; D044764:Ubiquitin-Activating Enzymes / Q000096:biosynthesis; D014470:Umbilical Cord / Q000166:cytology* / Q000378:metabolism*; D059631:Wharton Jelly / Q000166:cytology*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D051025:bcl-Associated Death Protein / Q000096:biosynthesis
chemical_list: C502778:ATG5 protein, human; D051017:Apoptosis Regulatory Proteins; D000071187:Autophagy-Related Protein 5; C491997:BECN1 protein, human; C107489:BIRC5 protein, human; D000071186:Beclin-1; D002457:Cell Extracts; D017077:Culture Media, Conditioned; D051034:Inhibitor of Apoptosis Proteins; C502070:MAP1LC3B protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes