Levels of IL-1 beta control stimulatory/inhibitory growth of cancer cells.
Different cellular signaling pathways operate in response to varying levels of IL-1 beta leading to genotoxic damage, cell apoptosis or cell growth. At high levels of IL-1 beta, cells receiving genotoxic insults engage apoptotic pathways. The IL-1 beta over expressing stable MCF7 cell secreting high level of IL-1 beta peptides undergo cell apoptosis. Cotreatment with an inhibitor of IL-1 beta and TNF-alpha synthesis prevented stilbene estrogen-induced lesions. In addition to direct effect of 17 beta-estradiol (E2) on mitochondria and redox cycling of catechol estrogens, E2-induced overexpression of IL-1 beta can produce an increase in the level of ROS. Our recent data showed that MCF7 cell growth and cyclin D1 expression are suppressed by antioxidants and mitochondrial blockers. Stably IL-1 beta transfected cells secreting moderate level of IL-1 beta peptides stimulated the clonal expansion of MCF7 cells. These studies support that in addition to ovarian estrogens, mitogenic signals may also come from TNF-alpha and IL-1 beta-generated O2*- and hydrogen peroxide. Further validation of this concept that the concentrations of the peptide interleukin-1 beta within the cells determine its stimulatory or inhibitory signals regulating the growth of estrogen-dependent tumors might result in novel preventive strategies.
Roy
Deodutta
D
Department of Environmental and Occupational Health, Robert Stempel School of Public Health, Florida International University, Miami, FL 33199, USA. Droy@fiu.edu
Sarkar
Shubhashish
S
Felty
Quentin
Q
D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D007375:Interleukin-1 / Q000378:metabolism / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009389:Neovascularization, Pathologic; D010053:Ovary / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D017382:Reactive Oxygen Species; D015398:Signal Transduction
D016207:Cytokines; D004967:Estrogens; D007375:Interleukin-1; D010455:Peptides; D017382:Reactive Oxygen Species; D004958:Estradiol; D006861:Hydrogen Peroxide; D010100:Oxygen