title: Sodium salicylate switches glucose depletion-induced necrosis to autophagy and inhibits high mobility group box protein 1 release in A549 lung adenocarcinoma cells.
abstract: 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.
authors.affiliation: Research Center for Resistant Cells, College of Medicine, Chosun University, Gwangju 501-759, Korea.
authors.forename: Sung-Chul
authors.initials: SC
authors.lastname: Lim
authors.forename: Sun Mi
authors.initials: SM
authors.lastname: Kim
authors.forename: Jeong Eun
authors.initials: JE
authors.lastname: Choi
authors.forename: Cho Hee
authors.initials: CH
authors.lastname: Kim
authors.forename: Hong-Quan
authors.initials: HQ
authors.lastname: Duong
authors.forename: Song Iy
authors.initials: SI
authors.lastname: Han
authors.forename: Ho Sung
authors.initials: HS
authors.lastname: Kang
mesh_terms: 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
chemical_list: 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