Meeting Report Apoptosis in Greece Sergio A. Lamprecht 1 and John D. Delinassios 2 1 Gastroenterology Department, Soroka Medical Center and Department of Clinical Biochemistry, Ben-Gurion University of the Negev, Beer Sheva, Israel 2 International Institute of Anticancer Research, Athens, Greece International Conference on Apoptosis Athens, Greece, October 2 – 5, 1997 Abbreviations: TGF-b, transforming growth factor-beta; PKC, protein kinase C; NSAIDS, Nonsteroidal anti-inflammatory drugs; COX, cyclooxygenase; GI, gastrointestinal; Bcl-2, B-cell lymphoma/leukemia-2 protein; EM, electron microscopy; ROS, reactive oxygen species; Bax, Bcl-2-associated x-protein; NFkB, nuclear factor kB; IIAR, International Institute of Anticancer Research; SSCP, single-strand conformational polymorphism The International Conference on Apoptosis was held in the International Institute of Anticancer Research (Athens, Greece) from October 2 – 5 1997. The program consisted of main lectures, short talks, a session devoted to research aims and poster presentations, all of which covered a wide interdisciplinary spectrum of apoptosis research. Here we survey the salient features of the conference. No attempt was made to cover all the speakers and poster sessions. The session devoted to the biochemical mechanisms of apoptosis began with an incisive talk by S. Dormann (Freiburg, Germany). The Freiburg team, headed by G. Bauer, has provided vast evidence that TGF-b synthesized by transformed fibroblasts triggers nontransformed homo- typic cells to release a short-lived apoptosis-inducing factor (or factors) specifically directed against transformed cells. Dormann elegantly discussed the distinct but interrelated roles of TGF-b in the lethal cell dialogue. A most interesting observation was that TGF-b causes downmodulation of endogenous survival factors in the transformed cells. This finding not only re-emphasizes the importance of context in defining TGF-b pleiotropic actions, but also proposes a novel mechanism of apoptosis induction. A. Dvilansky (Beer Sheva, Israel) presented solid evidence that in a number of human leukemic cell lines the antitumoral growth-restraining action of non-steroidal antiestrogens (e.g., nafoxidine) is associated with the induction of apoptosis. The effects of the drugs was abrogated by antioxidants. Data were shown suggesting a contributory role of PKC in the apoptotic process. Of late, much attention is focused on the role of mitochondria in the apoptotic suicide pathway. P. Schotte (Ghent, Belgium) presented convincing findings indicating that the decrease of mitochondrial transmembrane potential releases a factor able to induce apoptosis in isolated nuclei. The apoptogenic mitochondrial agent triggers the proces- sing of caspase 3 and caspase 11 with subsequent activation of the ICE-like proteases. These data substan- tiated by an elegant series of experiments strengthen the recurring observation of an intimate relationship between mitochondria and the caspase system in apoptosis. The results indicate that caspases’ activity is located down- stream to the mitochondrial apoptotic response. Intense interest is centered on non-steroidal anti- inflammatory drugs such as aspirin and sulindac as chemopreventive agents against colorectal cancer. Convin- cing evidence is available showing that these drugs induce apoptosis in colonic cells. D.J.E. Elder (Bristol, U.K.) reviewed incisively the present knowledge pertaining to the NSAIDs-COX system. He reported findings on the inducible form COX-2 which, while promoting colon carcinogenesis, is inhibited by NASAIDs with very low GI toxicity. The effect of the COX-2 selective inhibitor NS-398 was examined on two colorectal carcinoma cell lines, one expressing constitutively COX-2 (HT-29), the other appar- ently devoid of enzyme activity (S/KS). Both lines do not express wild-type p53. The results clearly expounded showed that NS-398 induces apoptosis in both cell lines. This action was p53-independent and surprisingly did not require the presence of the COX-2 protein. How then does the COX-2 inhibitor exert its apoptotic, antineoplastic action? The afternoon session pertaining to cellular and molecular biology of apoptosis began with an introductory lecture by S. Lamprecht (Beer Sheva, Israel) aptly entitled ‘apoptosis alive today.’ Lamprecht examined in detail our present understanding of the apoptosis process trying to identify a central, nodal step of no-return where ineluctable execution of apoptosis takes place, irrespective of the disparate initial stimuli, whether stochastic or determined. Inevitably this inquiry led to an examination of the caspase family. He argued that the promiscuous presence of the caspase zymogens in nuclei, cytoplasm and possibly in mitochondria is too perilous, with the stage set for an accidental and catastrophic amplifying cascade. We there- fore miss some critical information on stringent regulatory devises which normally prevent unscheduled caspase activation. Lamprecht also expressed doubts as to whether the life and death of a cell simply relies on a stoichiometic relationship between various proteins of the bcl-2 family, finding this control mechanism, albeit economical for the cell, too ‘coarse’ for determining the cell fate. In a separate talk, he also presented recent findings from his laboratory Cell Death and Differentiation (1998) 5, 337 – 339  1998 Stockton Press All rights reserved 13509047/98 $12.00 http://www.stockton-press.co.uk/cdd