406 ANN IST SUPER SANITà 2007 | V OL. 43, NO. 4: 406-416 RESEARCH FROM ANIMAL T ESTING TO CLINICAL EXPERIENCE Summary. Polyphenols have been demonstrated to have clear antioxidant activities in vitro. However, in complex biological systems, they exhibit additional properties which are yet poorly understood. Apoptosis is a genetically controlled and evolutionarily conserved form of cell death of critical importance for the normal embryonic development and for the maintenance of tissue homeostasis in the adult organism. The malfunction of the death machinery may play a primary role in various pathologic processes, leading to proliferative or degenerative diseases. Polyphenols can directly in- teract with speciic steps and/or proteins regulating the apoptotic process in different ways depend- ing on their concentration, the cell system, the type or stage of the pathological process. A growing body of in vitro evidence has provided interesting insights in the comprehension of the cellular and molecular mechanisms responsible for the modulation of apoptosis. However additional and harder studies are needed to better elucidate the mechanisms of action and the real in vivo effectiveness of polyphenols in order to propose them as potential candidates for chemoprevention and treatment of cancer and cardiovascular diseases. Key words: polyphenols, apoptosis, carcinogenesis, atherosclerosis. Riassunto (Apoptosi nel cancro e nell’aterosclerosi: l’attività dei polifenoli). I polifenoli risultano possedere spiccate proprietà antiossidanti in vitro. Tali composti, comunque, mostrano ulteriori funzioni, ancora poco conosciute, in sistemi biologici complessi. L’apoptosi è un processo ordinato di morte cellulare geneticamente controllato presente negli organismi viventi e conservato durante l’evoluzione. Essa ha un importante ruolo durante lo sviluppo embrionale e accompagna l’organi- smo nell’intero arco della vita controllando il delicato equilibrio cellulare a livello di organi e tessuti. L’alterato funzionamento del processo apoptotico può favorire l’insorgere di patologie proliferative o degenerative. I polifenoli sono in grado di agire direttamente sulle singole fasi e/o singole proteine inluenzando il processo apoptotico in modi diversi che dipendono dalla loro concentrazione, dal tipo cellulare utilizzato e dal tipo o fase del processo patologico studiato. Evidenze sperimentali hanno contribuito ad ampliare la comprensione dei meccanismi d’azione dei polifenoli. Ulteriori ed approfonditi studi dovranno comunque provare la loro reale eficacia in vivo, al ine di proporli come potenziali candidati per la prevenzione e cura sia del cancro che delle malattie cardiovascolari. Parole chiave: polifenoli, apoptosi, carcinogenesi, aterosclerosi. Apoptosis in cancer and atherosclerosis: polyphenol activities Claudio Giovannini, Beatrice Scazzocchio, Rosaria Varì, Carmela Santangelo, Massimo D’Archivio and Roberta Masella Centro Nazionale per la Qualità degli Alimenti e per i Rischi Alimentari, Istituto Superiore di Sanità, Rome, Italy INTRODUCTION Cancer and coronary heart disease are the most important disorders that cause alarming mortality and morbility in humans. Research efforts of the last 30 years have shown that dietary habits and lyfestyle may reduce their risk. Many foods because of their components, may provide protection against a vari- ety of pathologies characterized by oxidative stress, including cancer and CVDs [1]. In particular it is well known that fruits and vegetables, rich in antioxidant compounds, are involved in prevention and protec- tion against degenerative chronic diseases which are characterized by ROS overproduction and dysregu- lated apoptosis. Apoptosis is a genetically controlled and evolutionarily conserved form of cell death of critical importance for normal embryonic develop- ment and for the maintenance of tissue homeostasis in the adult organism [2]. The malfunction of the death machinery may play a primary or secondary role in various diseases, with essentially too little or too much apoptosis leading to proliferative or de- generative diseases, respectively. The machinery re- sponsible for killing and degradation of the cell via apoptosis become activated through various stimuli. In addition, cell signalling pathways, mitogenic and stress responsive pathways are involved in the regu- lation of apoptotic signalling [3]. The ine-tuning of the balance between the pro- and anti-apoptotic fac- Indirizzo per la corrispondenza (Address for correspondence): Claudio Giovannini, Centro Nazionale per la Qualità degli Alimenti e per i Rischi Alimentari, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. E-mail: clagiovn@iss.it.