ANTI-CANCER AND OXIDANT PROPERTIES OF DIFFERENT SESQUITERPENE LACTONES ISOLATED FROM INDIGENOUS LEBANESE PLANTS
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| Title | ANTI-CANCER AND OXIDANT PROPERTIES OF DIFFERENT SESQUITERPENE LACTONES ISOLATED FROM INDIGENOUS LEBANESE PLANTS |
| Authors | |
| Abstract | Most cancers are of epithelial origin of which skin cancer is the most frequent. Numerous naturally occurring compounds have been identified as skin chemopreventive agents, and many of the best-selling anticancer drugs are plant-derived. While screening for anti-cancer activities of forty-four Middle Eastern plant extracts used in folk medicine, we identified the Lebanese indigenous plants, Centaurea ainetensis and Achillea falcata, to possess potent and selective activities against cancer cells. Bioassay-guided fractionation of these plants’ crude extracts led to the isolation of the sesquiterpene lactone family of plant secondary metabolites having the most potent anti-tumor activities. These included two guaianolides from C. ainetensis: Salograviolide A (Sal-A) and its hydroxy-isomer and four seco-guanolide derivatives from A. falcata: Tanaphillin, 3-beta-methoxy-3-deshydroxy-iso-seco-tanapartholide (beta-Tan), iso-seco-tanapartholide, and 8-hydroxy-3-methoxy-iso-seco-tanaparatholide. We determined the growth inhibitory effects of the isolated sesquiterpene lactones on the human epidermal HaCaT cells, a well characterized model for early stage skin carcinogenesis, and correlated these activities with oxidant potential. We found that Sal-A and beta-Tan exhibited the most potent growth inhibitory effects at concentrations that were not cytotoxic to primary human keratinocytes. Sal-A caused pre-G0/G1 cell cycle arrest and reduced cyclin D1 proteins while beta-Tan induced G2/M arrest and decreased cyclin B1 proteins. Sal-A- and beta-Tan-induced growth inhibition was preceded by an early and progressive accumulation of reactive oxygen species (ROS). Pre-treatment with different anti-oxidants reduced drug-induced ROS generation and abrogated growth inhibition. These studies provide a rationale for designing plant-derived anti-cancer drugs from sesquiterpene lactones. |
| Publisher | African Ethnomedicines Network |
| Date | 2009-06-07 |
| Source | African Journal of Traditional, Complementary and Alternative medicines (AJTCAM) ABSTRACTS OF THE WORLD CONGRESS ON MEDICINAL AND AROMATIC PLANTS, CAPE TOWN NOVEMBER 2008 |
| Rights | Articles can be used for educational and non-comercial purposes. The copyrights of articles are retained by the authors with publication rights granted to AJTCAM. |