Ethyl pyruvate induces necrosis-to-apoptosis switch and inhibits high mobility group box protein 1 release in A549 lung adenocarcinoma cells.
Ethyl pyruvate (EP), a stable lipophilic pyruvate derivative, has been shown to exert anti-inflammatory activities through inhibiting the expression of various pro-inflammatory mediators as well as circulating levels of high mobility group box protein 1 (HMGB1) in a variety of in vitro and in vivo model systems. Necrotic cell death triggers an inflammatory response through release of HMGB1 in the extracellular space due to the membrane rupture. In an effort to better understand the pharmacological action mechanism that could explain the anti-inflammatory properties of EP, we examined the effects of EP on necrotic cell death in A549 lung adenocarcinoma cells in response to glucose deprivation (GD), a common characteristic of the tumor microenvironment. Here we show that EP prevented GD-induced necrosis and HMGB1 release and switched the cell death mode to apoptosis through inhibiting GD-induced CuZn superoxide dismutase release and ROS production. These results suggest that the necrosis-to-apoptosis switch activity of EP may contribute to its anti-inflammatory action and that EP may suppress tumor development possibly through its activity to induce the cell death mode switch from tumor promoting necrotic cell death to tumor suppressive apoptotic cell death.
Lim
Sung-Chul
SC
Research Center for Resistant Cells, Department of Pathology, College of Medicine, Chosun University, Gwangju 501-759, Korea.
Choi
Jeong Eun
JE
Kim
Cho Hee
CH
Duong
Hong-Quan
HQ
Jeong
Gui-Ae
GA
Kang
Ho Sung
HS
Han
Song Iy
SI
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009336:Necrosis / Q000378:metabolism; D011773:Pyruvates / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D024243:HMGB1 Protein; D011773:Pyruvates; D017382:Reactive Oxygen Species; C046522:ethyl pyruvate; D013482:Superoxide Dismutase; D005947:Glucose