Biomed & Pharmacother 1999 ; 53 : 315-8 0 Elsevier, Paris Dossier: Aspirin Aspirin induced apoptosis in gastric cancer cells B.C.Y. Wong, G.H. Zhu, S.K. Lam Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China Summary -Aspirin has been well known for its anti-pyretic and anti-inflammatory action over the past century. Its main action in the gas- tro-intestinal tract has always been associated with erosion and ulceration. However in recent years, there has been evidence suggesting that aspirin and the more potent non-steroidal anti-inflammatory drugs (NSAIDs), could reduce the risk of gastric and colon cancer. One of the possible mechanisms in chemo-prevention is the ability to induce apoptosis in epithelial cells of the gastro-intestinal origin. This article introduces the role of apoptosis in the body and the gastro-intestinal tract. Evidence on the chemo-preventive role of aspirin and NSAIDs are listed, and the mechanisms of action discussed. 0 1999 Elsevier, Paris apoptosis I aspirin I cyclooxygenase / gastric cancer Aspirin hasclinical benefits related to its anti-platelet activity, anti-pyretic, and anti-inflammatory actions.It has also been known to be associated with gastro- intestinal side-effects, mainly in the form of gastric and duodenal ulcerations or erosions. However recently, there are data to suggest that aspirin is not always harmful to the gastro-intestinal tract, but instead is able to reduce the risk of gastric and colon cancer. The mechanism may be associated with alter- ations of the processcalled apoptosisin the gastro- intestinal epithelium. We present some of the recent evidence concerning the role of aspirin in gastro- intestinal cancer prevention and the underlying mech- anismof apoptosis. APOPTOSIS Apoptosis, also known as programmedcell death, is a form of genetically regulated cell death under tight control. It is recognized and differentiated from necro- sisby distinct morphological and biochemical features [ 1, 21.This form of active cell death is found in all tis- sues, including gastro-intestinal epithelium, and can be induced by a wide variety of physiological and patho- logical stimuli. In the physiological state,there is a bal- ancebetweenproliferation and apoptosis. Cell loss via apoptosis does not produce inflammation, in contrastto cell death by necrosis, and therefore it does not induce any harm to the surrounding structures. Besides the regulation of physiological cell turnover, the important function of apoptosis is the removal of damaged cells with mutated DNA. This prevents the proliferation of malignant clones or the propagationof cells containing viral DNA [3]. Deregulation of the apoptosis pathway can lead to diseases (most notably cancers), auto- immune diseases, and neurodegenerative disorders [4, 51.The role of apoptosis in a wide variety of diseases, together with its highly regulated nature, has made it an attractive new target for therapeutic intervention in diseases previously considered incurable, especially cancer. Apoptotic cell death occurs in two phases: an initial commitment to cell death, followed by an execution phase characterized by morphological changes in cell structure. Cells of different organs, and more or less of different species, have common execution machinery. The external agentsthat trigger apoptosis include, but not exclusively, toxic chemicals, ultraviolet irradiation, chemotherapeutic agents, growth factor withdrawal, and tumor necrosis factors. These signalsact through cell surfacereceptorsor ligands and are transmitted to the cytosol and nucleus by signal transduction path- ways. Activation of the caspase family beginsthe exe- cution phase.Caspases are cysteine proteases which cleave critical cellular substrates and precipitate the dramatic morphological changes of apoptosis,first in mitochondria and the nucleus, and then followed by changes in the cell membrane.