title: Methylselenol, a selenium metabolite, plays common and different roles in cancerous colon HCT116 cell and noncancerous NCM460 colon cell proliferation.
abstract: Methylselenol is hypothesized to be a critical selenium metabolite for anticancer action, and differential chemopreventive effects of methylselenol on cancerous and noncancerous cells may play an important role. In this study, the submicromolar concentrations of methylselenol were generated by incubating methionase with seleno-L methionine, and colon-cancer-derived HCT-116 cells and noncancerous colon NCM460 cells were exposed to methylselenol. Methylselenol exposure inhibited cell growth and led to an increase in G1 and G2 fractions with a concomitant drop in S-phase and an induction of apoptosis in HCT116, but to a much lesser extent in NCM460 colon cells. Similarly, the examination of mitogen-activated protein kinase (MAPK) and cellular myelocytomatosis oncogene (c-Myc) signaling status revealed that methylselenol inhibited the phosphorylation of extracellular-regulated kinase1/2 and p38 mitogen-activated protein kinase and the expression of c-Myc in HCT116 cells, but also to a lesser extent in NCM460 cells. The other finding is that methylselenol inhibits sarcoma kinase phosphorylation in HCT116 cells. In contrast, methylselenol upregulated the phosphorylation of sarcoma and focal adhesion kinase survival signals in the noncancerous NCM460 cells. Collectively, methylselenol's stronger potential of inhibiting cell proliferation/survival signals in the cancerous HCT116 cells when compared with that in noncancerous NCM460 cells may partly explain the potential of methylselenol's anticancer action.
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota 58202-9034, USA. huawei.zeng@ars.usda.gov
authors.forename: Huawei
authors.initials: H
authors.lastname: Zeng
authors.forename: Mary
authors.initials: M
authors.lastname: Briske-Anderson
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Mary P
authors.initials: MP
authors.lastname: Moyer
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003106:Colon / Q000166:cytology / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D000432:Methanol / Q000031:analogs & derivatives* / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016566:Organoselenium Compounds / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016196:S Phase / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016566:Organoselenium Compounds; D016271:Proto-Oncogene Proteins c-myc; C019003:methaneselenol; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000432:Methanol