Sodium salicylate switches glucose depletion-induced necrosis to autophagy and inhibits high mobility group box protein 1 release in A549 lung adenocarcinoma cells.
Sodium salicylate, the active metabolite of aspirin, has been shown to exert anti-inflammatory activities by inhibiting the expression of various pro-inflammatory factors, and has potent anti-cancer effects against a number of human cancers including colon, lung, breast and leukemia. Necrotic cell death is emerging as one of the crucial factors that trigger an inflammatory response since during necrotic death the cell membrane is ruptured and the intracellular constituents including high mobility group box 1 (HMGB1) are released into the extracellular space, thereby activating an inflammatory response. In contrast, autophagic death is regarded as a form of tumour suppressive cell death, as indicated in tumour suppressors such as beclin 1 in autophagic pathways. To better understand the anti-inflammatory properties of sodium salicylate and its effect on necrotic cell death in A549 cells induced by glucose depletion (GD), a common characteristic of the tumour micro-environment, was examined. While GD induced mostly necrotic death in A549 cells, salicylate suppresssed GD-induced necrosis and HMGB1 release. In addition, salicylate shifted the cell death pattern to autophagy by inhibiting GD-induced Cu/Zn superoxide dismutase release and ROS production. These results indicate that the activity of salicylate to prevent necrotic death may contribute to its anti-inflammatory action and suppress tumour development possibly through switching the cell death mode from tumour-promoting necrotic cell death to tumour-suppressive autophagic cell death.
Lim
Sung-Chul
SC
Research Center for Resistant Cells, College of Medicine, Chosun University, Gwangju 501-759, Korea.
Kim
Sun Mi
SM
Choi
Jeong Eun
JE
Kim
Cho Hee
CH
Duong
Hong-Quan
HQ
Han
Song Iy
SI
Kang
Ho Sung
HS
D000230:Adenocarcinoma / Q000378:metabolism*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001343:Autophagy; D001562:Benzimidazoles / Q000494:pharmacology; D045744:Cell Line, Tumor; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism*; D024243:HMGB1 Protein / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000196:embryology*; D009336:Necrosis; D012980:Sodium Salicylate / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D001562:Benzimidazoles; D016861:Cyclooxygenase Inhibitors; D024243:HMGB1 Protein; D013778:Tetrazolium Salts; D013844:Thiazoles; D013482:Superoxide Dismutase; C022616:thiazolyl blue; D005947:Glucose; C017807:bisbenzimide ethoxide trihydrochloride; D012980:Sodium Salicylate