Selenomethionine stimulates MAPK (ERK) phosphorylation, protein oxidation, and DNA synthesis in gastric cancer cells.
Selenium is an essential trace element and is required for the synthesis of cellular enzymes that protect against oxidative stress. Epidemiological findings indicate that low selenium intake is associated with increased cancer risk, and, although the majority of studies show that exposure of transformed cells to selenium results in apoptotic cell death, there are reports indicating that cells exposure to low selenium concentrations promotes cellular proliferation. Gastric adenocarcinoma SNU-1 cells responded to selenomethionine with a biphasic proliferative curve: enhanced incorporation of 3H-thymidine into DNA within a very narrow range of selenomethionine concentrations followed by decreased 3H-thymidine uptake at higher levels. Concentrations of selenomethionine that stimulate cellular proliferation also induce cellular oxidation and phosphorylation of MAPK (ERK), a component of cell signaling cascades. MAPK (ERK) phosphorylation is synonymous with MAPK activation and enhanced cell growth. Our findings support previous observations of enhanced proliferation in response to low levels of selenium and suggest that, at certain concentrations, selenomethionine induces mild oxidative stress that, in turn, stimulates DNA synthesis.
Verma
Archana
A
Department of Medicine, Division of Gastroenterology, Cook County Hospital, Chicago, IL 60612, USA.
Atten
Mary Jo
MJ
Attar
Bashar M
BM
Holian
Oksana
O
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D012645:Selenomethionine / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000473:pathology*; D014407:Tumor Cells, Cultured
D004247:DNA; D012645:Selenomethionine; D020929:Mitogen-Activated Protein Kinase Kinases