Hypothesis: the antitumor activities of statins may be mediated by IL-18.
Statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase, are thought to reduce the risk of cancer through the inhibition of Ras farnesylation and serum lipid level. A pleiotropic proinflammatory cytokine, interleukin-18 (IL-18), is reported to exhibit significant antitumor activities through the activation of cytotoxic T lymphocytes and natural killer cells and the inhibition of angiogenesis. Previously, we found that pravastatin, fluvastatin, and simvastatin induced the production of IL-18 in human monocytes. The addition of mevalonate abolished the IL-18 production induced by pravastatin, fluvastatin, and simvastatin, indicating that the IL-18 production might be a result of the inhibition of HMG-CoA reductase. We present a new hypothesis that the production of IL-18 might play roles in the action of statins on cancer.
Takahashi
Hideo Kohka
HK
Weitz-Schmidt
Gabriele
G
Iwagaki
Hiromi
H
Yoshino
Tadashi
T
Tanaka
Noriaki
N
Nishibori
Masahiro
M
D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D020382:Interleukin-18 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008798:Mevalonic Acid / Q000494:pharmacology; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000517:prevention & control*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020382:Interleukin-18; D008798:Mevalonic Acid