| Autor: |
Cui, B., Lee, Y. H., Chai, H., Tucker, J. C., Fairchild, C. R., Raventos-Suarez, C., Long, B., Lane, K. E., Menendez, A. T., Beecher, C. W. W., Cordell, G. A., Pezzuto, J. M., Kinghorn, A. D. |
| Zdroj: |
Journal of Natural Products; November 29, 1999, Vol. 62 Issue: 11 p1545-1550, 6p |
| Abstrakt: |
Bioassay-directed fractionation of the flowers and leaves of Ratibida columnifera using a hormone-dependent human prostate (LNCaP) cancer cell line led to the isolation of 10 cytotoxic substances, composed of five novel xanthanolide derivatives (2−4, 7, and 8), a novel nerolidol derivative (9), and three known sesquiterpene lactones, 9α-hydroxy-seco-ratiferolide-5α-O-angelate (1), 9α-hydroxy-seco-ratiferolide-5α-O-(2-methylbutyrate) (5), 9-oxo-seco-ratiferolide-5α-O-(2-methylbutyrate) (6), as well as a known flavonoid, hispidulin (10). On the basis of its cytotoxicity profile, compound 5 was selected for further biological evaluation, and was found to induce G1 arrest and slow S traverse time in parental wild type p53 A2780S cells, but only G2/M arrest in p53 mutant A2780R cells, with strong apoptosis shown for both cell lines. The activity of 5 was not mediated by the multidrug resistance (MDR) pump, and it was not active against several anticancer molecular targets (i.e., tubulin polymerization/depolymerization, topoisomerases, and DNA intercalation). While these results indicate that compound 5 acts as a cytotoxic agent via a novel mechanism, this substance was inactive in in vivo evaluations using the murine lung carcinoma (M109) and human colon carcinoma (HCT116) models. |
| Databáze: |
Supplemental Index |
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