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Biological Characterization of the Chemical Structures of Naturally Occurring Substances with Cytotoxicity  

Park, Hee-Juhn (Division of Applied Plant Sciences, Sangji University)
Jung, Hyun-Ju (Division of Applied Plant Sciences, Sangji University)
Lee, Kyung-Tae (College of Pharmacy, Kyung-Hee University)
Choi, Jong-Won (College of Pharmacy, Kyungsung University)
Publication Information
Natural Product Sciences / v.12, no.4, 2006 , pp. 175-192 More about this Journal
Abstract
Screening for the cytotoxicity from plant origin is the first stage for anti-cancer drug development. A variety of terpenoids with exomethylene, epoxide, allyl, $\alpha,\beta-unsaturated$ carbonyl, acetylenes, and $\alpha-methylene-\gamma-lactone$ induces apoptosis and/or differentiation as well as cytotoxicity through the ROS signal transduction pathways. These are found among monoterpenes, sesquiterpenes, triterpenes, flavonoids, coumarins, diarylheptanoids, and even organosulfuric compounds. The most essential characteristics of natural cytotoxic substances is to possess the strong electrophilicity that is susceptible to nucleophilic biomolecules in the cell. Thiol-reductants and superoxide dismutase can block or delay apoptosis. Thus, ROS and the resulting cellular redox-potential changes can be parts of the signal transduction pathway during apoptosis. Disturbance of the balance of oxireduction by the pigment of natural quinones also caused the induction of the differentiation and apoptosis. Saponins with the cytotoxicity are restricted to their monodesmosides, rather than to bisdesmosides. Those saponins exhibited calcium ion-mediated apoptosis in addition to cytotoxicity whereas they showed also differentiation without extracellular calcium ion. The properties on cytotoxicity, apoptosis, and differentiation were assumed to depend on resultant oxidative stress to the cells. In this review, we describe a spectrum of cytotoxic compounds with various action mechanisms.
Keywords
cytotoxicity; natural products; apoptosis; differentiation; reactive oxygen species (ROS); oxidative stress;
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