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.
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