Cell death: Apoptosis versus necrosis (Review)

Abstract

. Cell death and the subsequent post-mortem changes, called necrosis, are integral parts of normal development and maturation cycle. Despite the importance of this process, the mechanisms underlying cell death are still poorly understood. In the recent literature, cell death is said to occur by two alternative, opposite modes: apoptosis, a programmed, managed form of cell death, and necrosis, an unordered and accidental form of cellular dying. The incorrect consequence is the overlapping of: a) the process whereby cells die, cell death; and b) the changes that the cells and tissues undergo after the cells die. Only the latter process can be referred to as necrosis and represents a 'no return' process in cell life. In this review, we discuss the excellent basic research developed in this field during last decades and problems that remain to be resolved in defining both experimentally and mechanicistically the events that lead to and characterize cell death. IntroductionCell death is part of normal development and maturation cycle, and is the component of many response patterns of living tissues to xenobiotic agents (i.e. micro organisms and chemicals) and to endogenous modulations, such as inflammation and disturbed blood supply (1,2). Cell death is an important variable in cancer development, cancer prevention and cancer therapy (3-5). In the treatment of cancer, the major approach is the removal, by surgery, of the neoplasm and/or the induction of cell death in neoplastic cells by radiation, toxic chemicals, antibodies and/or cells of the immune system (6-9). On the other hand, this pathobiological process remains poorly understood and the physiological and biochemical factors that lead to cell death are still not clear. One main factor is the existing confusion between 'apoptosis' process, as compared and contrasted with 'necrosis', leading to the overlapping of the ante mortem changes, i.e. the process of cell death, and the post-mortem changes, i.e. the necrosis process. The pathobiology of cell deathThe elegant scientific exploration of sub-cellular molecular anatomy of the last decades have reinforced the cell concept as 'the smallest integrating unit in biology: a pseudo-intelligent computer that receives, screens, changes, reacts to and adapts to a host of environmental signals, all of this activity apparently

Age-dependent cell death and the role of ATP in hydrogen peroxide-induced apoptosis and necrosis

“…A deficiency of ATP in these steps would prevent downstream processes, including caspase-3 activation. Consistent with results of previous studies showing that low intracellular levels of free ATP might permit apoptotic stimuli to induce necrosis (8,(23)(24)(25)(26), we found that a decrease in the intracellular ATP concentration, induced by inhibition of ATPase, glycolysis, or mitochondrial respiration activities, leads to suppression of caspase-3-like activity (Fig. 4B) and enhancement of cell necrosis (Fig.…”

Comparison of Caspase Genes for the Induction of Apoptosis Following Gene Delivery

“…Eradicating tumor cells could be achieved by inducing either apoptosis or necrosis. Apoptosis has advantages over necrosis, in that degradation products are packaged and will be rapidly cleared by phagocytosis, while necrosis involves cell leakage, inflammation, and bystander effects [3,4].…”

Tocotrienol inhibits proliferation of human Tenon’s fibroblasts in vitro: a comparative study with vitamin E forms and mitomycin C

“…In our in vitro study, any possible antiproliferative effect of α-tocopheryl succinate was strongly overlaid by its cytotoxic effects. Increased cytoplasmic granulation, cell swelling, and early plasma membrane leakage strongly pointed to simple primary necrosis [17]. In vivo, simple primary necrosis leads to inflammation of surrounding tissue.…”

“…As apoptosis does in general not provoke an inflammatory reponse in vivo [17], death of fibrolasts and inflammatory cells by apoptosis should be an acceptable event in the postoperative period, leading to reduction of scar tissue. However, complications such as bleb leak and infection may occur if the bleb tissue is too extensively devitalized.…”