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The thioredoxin system, composed of thioredoxin reductase (TrxR), thioredoxin (Trx), and NADPH (Nicotinamide adenine dinucleotide compounds were found to induce antiproliferative effects towards several human cancer cells some of which endowed with cisplatin or multidrug resistance. In addition, they were able to activate caspase-3 and induce apoptosis observed as nucleosome formation and sub-G1 cell accumulation. The complexes with thiocyanate and xanthate ligands were particularly effective in inhibiting thioredoxin reductase and inducing apoptosis.Pharmacodynamic studies in human ovarian cancer cells allowed for the correlatation of intracellular drug accumulation with TrxR inhibition that leads to the induction of apoptosis via the mitochondrial pathway.

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A thermophilic and thermostable P-galactosidase activity was purified to homogeneity from crude extracts of the archaebacterium Suljiulobus sovuturicus, by a procedure including ion-exchange and affinity chromatography. The homogeneous enzyme had a specific activity of 116.4 units/mg at 75 'C with o-nitrophenyl P-galactopyranoside as substrate. Molecular mass studies demonstrated that the S. solfataricus P-galactosidase was a tetramer of 240 Ifr S kDa composed of similar or identical subunits. Comparison of the amino acid composition of pgalactosidase from S. solfataricus with that from Eschevichia culi revealed a lower cysteine content and a lower Arg/Lys ratio in the thermophilic enzyme. A rabbit serum, raised against the homogeneous enzyme did not crossreact with P-galactosidase from E. coli. The enzyme, characterized for its reaction requirements and kinetic properties, showed a thermostability and thermophilicity notably greater than those reported for P-galactosidases from other mesopbilic and thermophilic sources. More recently, a new P-galactosidase activity has been identified in E. colicells with LacZ deletion selected for growth on lactose [6]. This enzyme, termed ebg for evolved pgalactosidases, has a subunit molecular mass of 120 kDa, very close to that of the LacZ enzyme. However, the ebg protein has a hexameric and not a tetrameric structure, and the two enzymes are not immunologically related.In recent years, p-galactosidase activities from various microbial sources have been purified and characterized for their physicochemical properties, reaction requirements and substrate specificities [l, 71. Thermostable p-galactosidases [S ~ 1 I] have received considerable attention because of their possible utilization in the industrial processing of lactose-contain-4,51.

An NAD+-dependent alcohol dehydrogenase (alcohol: NAD' oxidoreductase, EC 1.1 .l .l) was detected in cellular extracts of the extreme thermophilic archaebacterium Sulfolobus solfataricus. The enzyme was purified to homogeneity and shown to be a dimer with a native molecular mass of 71 kDa by sucrose gradient centrifugation and SDS electrophoresis.The enzyme has a broad substrate specificity that includes linear and branched primary alcohols, linear and cyclic secondary alcohols, linear and cyclic ketones and anisaldehyde.The enzyme has an extraordinary thermophilicity and a remarkable thermostability, and appears to have some properties and a structure different from those previously described for thermophilic alcohol dehydrogenases.Alcohol dehydrogenase is widely distributed in nature and has been found in many microorganisms, plant and animal tissues [l]. In addition to being present in multiple forms [2], alcohol dehydrogenases isolated from different sources show different substrate specificities. For example, the yeast enzyme can catalyse oxidation of a very limited range of acyclic primary and secondary alcohols [3], while horse liver alcohol dehydrogenase exhibits a broader specificity and catalyses even the oxidation of cyclic, aromatic and steroid alcohols [4].The potential biotechnological applications of these enzymes in stereospecific organic synthesis and in the production of high-added-value products [5 -91 has been limited by several factors and so investigation has continued in search of more stable enzymes with a broader specificity.The interest in enzymes from thermophilic and extreme thermophilic bacteria is justified by the fact that many enzymes isolated from these organisms are thermostable and capable of acting at high temperatures. On the other hand, their catalytic activity is low at moderate temperatures at which conventional enzymes are optimally active. Besides, these enzymes have been found to be not only stable to heat but also to common protein denaturants and organic solvents [lo, 111. An NADP +-dependent alcohol dehydrogenase, thermostable and exhibiting a high tolerance towards organic solvents, was isolated from the extreme thermophilic bacterium Thermoanaerobium brockii by Lamed and Zeikus 1121.In this paper we report the purification to homogeneity and the characterization of an NAD+-dependent alcohol deCorrespondence to M. Rossi,