[Fluvastatin induces apoptosis on human tongue carcinoma cell line HSC-3].
Statins, which are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, suppress cell proliferation and induce apoptosis in various cancer cell lines. However, the effects of statins in head and neck carcinoma have not been reported. In this study, we investigated the mechanism by which fluvastatin induces apoptosis in HSC-3 cells. An increase in caspase-3 activity was observed. The apoptosis induced by fluvastatin was inhibited by the addition of geranylgeranyl pyrophosphate (GGPP) to the cell culture. When we examined the survival signals at the time of apoptotic induction, we also found that fluvastatin had caused a remarkable decrease in the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Moreover, we also found that U0126, a MEK1/2 inhibitor, induces apoptosis in HSC-3 cells. These results suggested that fluvastatin induces apoptosis by inhibiting GGPP biosynthesis and consequently decreasing the level of phosphorylated ERK1/2. The results of this study also indicate that fluvastatin may be used as an anticancer agent for tongue carcinoma.
Fujiwara
Kimiko
K
Department of Pharmacy, Kinki University Hospital, Osakasayama City, Japan.
Tsubaki
Masanobu
M
Yamazoe
Yuzuru
Y
Nishiura
Saori
S
Kawaguchi
Takeru
T
Ogaki
Mitsuhiko
M
Nishinobo
Minori
M
Shimamoto
Kenji
K
Moriyama
Kenzo
K
Nishida
Shozo
S
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002070:Butadienes / Q000494:pharmacology; D002277:Carcinoma / Q000473:pathology*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011106:Polyisoprenyl Phosphates / Q000096:biosynthesis; D014062:Tongue Neoplasms / Q000473:pathology*
D000970:Antineoplastic Agents; D002070:Butadienes; D004791:Enzyme Inhibitors; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D009570:Nitriles; D011106:Polyisoprenyl Phosphates; C113580:U 0126; D000077340:Fluvastatin; D048049:Extracellular Signal-Regulated MAP Kinases; C002963:geranylgeranyl pyrophosphate