Retinoids regulate many biological processes, including differentiation, morphogenesis and cell proliferation. They are also important therapeutic agents, but their clinical usefulness is limited because of side effects. Retinoid activities are mediated by specific nuclear receptors, the RARs and RXRs, which can induce transcriptional activation through specific DNA sites or by inhibiting the transcription factor AP-1 (refs 12-15), which usually mediates cell proliferation signals. Because the two types of receptor actions are mechanistically distinct, we investigated whether conformationally restricted retinoids, selective for each type of receptor action, could be identified. Here we describe a new class of retinoids that selectively inhibits AP-1 activity but does not activate transcription. These retinoids do not induce differentiation in F9 cells but inhibit effectively the proliferation of several tumour cell lines, and could thus serve as candidates for new retinoid therapeutic agents with reduced side effects.

Aloe is a genus of medicinal plants with a notable history of medical use. Basic research over the past couple of decades has begun to reveal the extent of Aloe?s pharmaceutical potential, particularly against neoplastic disease. This review looks at Aloe, both the genus and the folk medicine, often being called informally ?aloes?, and delineates their chemistry and anticancer pharmacognosy. Structures of key compounds are provided, and their pharmacological activities reviewed. Particular attention is given to their free radical scavenging, antiproliferative, and immunostimulatory properties. This review highlights major research directions on aloes, reflecting the enormous potential of natural sources, and of the genus Aloe in particular, in preventing and treating cancer.

The ever-increasing emergence of the resistance of mammalian tumor cells to chemotherapy and its severe side effects reduces the clinical efficacy of a large variety of anticancer agents that are currently in use. Thus, despite the significant progress in cancer therapeutics in the last decades, the need to discover and to develop new, alternative, or synergistic anticancer agents remains. Cancer prevention or chemotherapy based on bioactive fractions or pure components derived from desert plants with known cancer-inhibiting properties suggests promising alternatives to current cancer therapy. Plants growing on low nutrient soils and/or under harsh climatic conditions, such as extreme temperatures, intense solar radiation, and water scarcity, are particularly susceptible to attack from reactive oxygen species and have evolved efficient antioxidation defense systems. The many examples of desert plants displaying anticancer effects as presented here indicates that the same defensive secondary metabolites protecting them against the harsh environment may also play a protective or a curative role against cancer, as they also do against diabetes, neurodegenerative, and other acute and chronic diseases. The present review highlights a plethora of studies focused on the antineoplastic properties of desert plants and their prinicipal phytochemicals, such as saponins, flavonoids, tannins, and terpenes. Although many desert plants have been investigated for their antitumor properties, there are many that still remain to be explored - a challenge for the prospective cancer therapy of the future.

A major challenge is the development of retinoids with selective biological activities. Recently, studies on retinoid response mechanisms indicate that retinoids activate two classes of nuclear receptor proteins, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). Here, we analyze the activity of a series of (E)- and (Z)-stilbenecarboxylic acids for gene transcriptional activation of the RARs and RXR-alpha to determine the optimum pharmacophore for receptor activation. The data obtained indicate that RAR and RXR response pathways can be separated by using the appropriate ligand. The conformations of (Z)-4-[2-(5-,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)prop en-1-yl]benzoic acid (Z)-4-[1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)propen-2-yl]benzoic acid were examined by experimental and theoretical methods to establish the appropriate conformation of the latter that specifically activated the retinoid RXR. A palladium(0)-catalyzed aryl bromide-arylboronic acid coupling under nonanhydrous conditions was used to construct a biaryl bond in the conformationally restricted retinoid 2'- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthaleny)biphenyl-4-c arboxylic acid, which had RXR activity.

The five regioisomeric bromotryptophans (BrTrps) play an important role in the life of sponges and lower marine invertebrates. These bromo-amino acids, which are formed by post-translational modifications, are not found in nature in their free state, but rather are involved in more complex structures. Any of the BrTrps can be part of a peptide, a cyclic peptide, an indole alkaloid, an ergot alkaloid, a macrocycle and others. The present review covers the synthesis, physical and spectroscopic properties of the five BrTrps. It also describes the many exiting pharmacological and biological activities played by the BrTrps and by various secondary metabolites containing brominated tryptophan moieties. Of special interest are cyclic peptides containing the 2-BrTrp unit, which were isolated from marine sponges e.g. konbamide, orbiculamide A, the various keramamides, jaspamide eusynstyelamide and more. Important families of non-cyclic peptides containing the 6-BrTrp, include the styelins, the conotoxins, the cathelicidins and several constrained macrocyclic peptides. Many marine secondary BrTrp-containing, non-peptidic metabolites also display a remarkable spectrum of bioactivities, which can be harnessed for therapeutic and other purposes. Examples are: barettin, bromotryptanthrin, tetraacetyl clionamide, cyclocinamide A, clavicipitic acid, various brominated beta-carbolines. In this review we have presented the various synthetic routes leading to the preparation of the five BrTrps and many of its derivatives. Also, we have introduced the reader to many synthetic routes leading to BrTrp-containing non-peptidic natural products. Although the functional role of the various compounds in the human body is only poorly understood, its effects were extensively studied. Almost all of these compounds exhibit important therapeutic properties e.g. antifungal, antimicrobial, antihelmintic, insecticidal ichthyotoxic and anticancer activity. In the present review attempts have been made to provide synopsis, synthesis and symbiosis of chemical and biological actions, which may provide future guidance and facilitate further research in this area.

l " desert plants l " steppic plants l " antidiabetic l " oxidative stress l " reactive oxygen species (ROS) l " hypoglycemic effect

Context: Phytochemicals are produced by desert plants to protect themselves against stressful environments. They have been shown to be useful in preventing and fighting adverse pathophysiological conditions and complex diseases, including cancer. Although many desert plants have been investigated for their antitumor properties, a large number of them still remain to be explored for possible therapeutic applications in oncologic diseases.

The ever-increasing occurrence of cancer and the severe side effects and limited efficacy of current cancer chemotherapy based on chemical drugs shift the attention toward drugs of plant origin. The Cactaceae family comprises more than 1500 species, but until recently only a few of them have been tested for their chemopreventive and anticancer attributes, leaving a wide unexplored area still waiting for researchers to investigate. Considering this fact, and also the promising results obtained with the relatively few plants of this family already tested, it should justly be expected that some plants of the Cactaceae family yet unexplored might possess outstanding anticancer attributes, exceeding those displayed by the plants already tested. This review presents in vitro and in vivo experimental evidence on cancer chemopreventive and therapeutic potential of bioactive phytoconstituents and extracts derived from cactus plants. It also examines the underlying biochemical and molecular mechanisms involved in the antineoplastic effects of plants of the Cactaceae family. Current limitation and future directions of research towards effective use of cacti to develop efficient and side effect-free future cancer-preventive and anticancer drugs are also discussed.