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Human Umbilical Cord Wharton's Jelly Stem Cell Conditioned Medium Induces Tumoricidal Effects on Lymphoma Cells Through Hydrogen Peroxide Mediation
Author(s) -
Lin Hao Daniel,
Fong ChuiYee,
Biswas Arijit,
Choolani Mahesh,
Bongso Ariff
Publication year - 2016
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25501
Subject(s) - lipid peroxidation , chemistry , superoxide dismutase , propidium iodide , catalase , apoptosis , superoxide , programmed cell death , glutathione peroxidase , biochemistry , oxidative stress , microbiology and biotechnology , biology , enzyme
Several groups have reported that human umbilical cord Wharton's jelly stem cells (hWJSCs) possess unique tumoricidal properties against many cancers. However, the exact mechanisms as to how hWJSCs inhibit tumor growth are not known. Recent evidence suggests that exposure of cancer cells to high hydrogen peroxide (H 2 O 2 ) levels from H 2 O 2 ‐releasing drugs causes their death. We therefore explored whether the tumoricidal effect of hWJSCs on lymphoma cells was mediated via H 2 O 2 . We first exposed lymphoma cells to six different molecular weight cut‐off (MWCO) concentrates of hWJSC‐conditioned medium (hWJSC‐CM) (3, 5, 10, 30, 50, 100 kDa) for 48 h. Since, the 3 kDa‐MWCO concentrate showed the greatest cell inhibition we then investigated whether the tumoricidal effect of the specific 3 kDa‐MWCO concentrate on two different lymphoma cell lines (Ramos and Toledo) was mediated via accumulation of H 2 O 2 . We used a battery of assays (MTT, propidium iodide, mitochondria membrane potential, apoptosis, cell cycle, oxidative stress enzymes, hydrogen peroxide, mitochondrial superoxide, hydroxyl radical, peroxynitrile anion, and lipid peroxidation) to test this mechanism. The hWJSC‐CM‐3 kDa MWCO concentrate significantly decreased cell viability and mitochondrial membrane potential and increased cell death and apoptosis in both lymphoma cell lines. There were significant increases in superoxide dismutase with concomitant decreases in glutathione peroxidase, catalase, and thioredoxin peroxidase activities. H 2 O 2 levels, mitochondrial superoxide, hydroxyl radical, peroxynitrile anion, and lipid peroxidation were also significantly increased in both lymphoma cell lines. The results suggested that the hWJSC‐CM‐3 kDa MWCO concentrate regulates cellular H 2 O 2 leading to a tumoricidal effect and may thus be a promising anti‐lymphoma agent. J. Cell. Biochem. 117: 2045–2055, 2016. © 2016 Wiley Periodicals, Inc.