
Full text loading...
In continuatin of the previous issue, part II of the issue "Small molecules of natural origin for cancer therapy and chemoprevention" comprises of the following chapters. 3. From Pharmacogenomics and -proteomics to systems biology The recently developed genomic and proteomic technologies are thriving and fertilize many disciplines of life sciences, including pharmaceutical biology and pharmacognosy. The prospect is fascinating to gain mechanistic insights, how small molecules from natural origin act against cancer cells. The next wave - the construction of signalling and metabolic pathways with the help of data obtained from "-omics" technologies - is the task of systems biology, which will add another dimension to current pharmacology. Gabriele Zybarth and Nikolai Kley (Waltham, MA, USA) report the recent achievements in the field of genomics and proteomics, e.g., genome-wide transcription-profiling, genotyping of polymorphisms to predict drug efficacy, knock-out technology, chemical proteomics, target engineering, drug resistance and others. The chemical genomics-based target identification using anti-angiogenic agents as example is described by Ho Jeong Kwon (Seoul, Korea). Small molecules chemically synthesized or taken from natural sources are used to elucidate biological mechanisms and as lead compounds for the directed optimization of chemical compounds with drug-like properties. Sophisticated bioinformatics tools are applied to make this approach rapid and efficient. In analogy to classical genetics, one can distinguish forward from reverse chemical genomics. The forward approach aims to identify small molecule-induced cellular phenotypes and molecular target proteins affected. By reverse genomics, validated target proteins are used to searches for small molecules, which modulate the function of the target molecules. The article on artemisinin and its derivatives by Thomas Efferth (Heidelberg, Germany) gives a comprehensive overview of molecular pharmacology and pharmacogenomics of this drug class for anti-cancer treatment. Artemisinin is the active principle of the Chinese herb, Artemisia annua L., which shows profound cytotoxicity to cancer cells in addition to its anti-malarial properties. 4. Chemoprevention Chemopreventive agents inhibit the development of cancer, whereas chemotherapeutics are used to treat already established cancers. Since mechanisms of carcinogenesis frequently affect effectiveness of chemotherapy too, compounds which prevent carcinogenesis might also improve responsiveness of tumor cells to anti-tumor drugs. Dominique Delmas, Allan Lançon, Didier Colin, Brigitte Jannin and Norbert Latruffe (Dijon, France) report on resveratrol as promising chemopreventive agent. The beneficial effects of wine are associated with the physiological protection conferred by phenolic compounds such as resveratrol. It is a chemopreventive compound with multi-facetted features. It acts anti-carcinogenic, anti-angiogenic, anti-invasive, anti-metastatic, activates programmed cell death, arrests the cell cycle, and inhibits signal transduction pathways. Whereas it is not cytotoxic itself, it enhances the anti-tumor effect of anticancer drugs. Melinda C. Myzak and Roderick H. Dashwood (Corvallis, OR, USA) give an introduction in the field of histone deacetylases as targets for dietary cancer preventive agents and explain the relevance of aberrant histone acetylation for tumorigenesis. The authors also introduce the reader to histone deacetylase inhibitors of natural origin with chemopreventive activity and point to molecular mechanisms of action. Three examples are discussed in more detail, butyrate, diallyl disulfide, and sulphoraphane, all of which are constituents of relevant nutrients. 5. Biotechnology: plant cell culture for sustainable production of plant-derived drugs The knowledge on natural compounds and their molecular modes of action in cancer cells represents one side of the coin. The other side is the production of drugs for treatment of patients. There is an increasing demand in medicinal plants worldwide, most of which are collected from the wild. Although cultivation of medicinal plants is getting.........