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Cytotoxic sesquiterpenoids from Ratibida columnifera
1Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Journal of Natural Products
|December 2, 1999
Summary
Cytotoxic compounds from Ratibida columnifera flowers and leaves were identified. Compound 5 induced cell cycle arrest and apoptosis in cancer cells via a novel mechanism, though it lacked in vivo efficacy.
Area of Science:
- Natural Products Chemistry
- Pharmacology
- Cancer Biology
Background:
- Ratibida columnifera (prairie coneflower) is a plant with potential medicinal properties.
- Natural products are a rich source of novel anticancer agents.
Purpose of the Study:
- To isolate and characterize cytotoxic compounds from Ratibida columnifera.
- To evaluate the anticancer potential and mechanism of action of isolated compounds.
Main Methods:
- Bioassay-directed fractionation of plant extracts using LNCaP cells.
- Isolation and structural elucidation of cytotoxic compounds using spectroscopic methods.
- In vitro cell cycle analysis, apoptosis assays, and mechanism of action studies.
Main Results:
- Ten cytotoxic substances were isolated, including five novel xanthanolide derivatives, one novel nerolidol derivative, and known compounds.
- Compound 5 induced G1 arrest in wild-type p53 cells and G2/M arrest in p53-mutant cells, leading to apoptosis.
- Compound 5's activity was independent of the multidrug resistance pump and did not target common anticancer pathways.
Conclusions:
- Ratibida columnifera contains novel cytotoxic compounds with potential anticancer activity.
- Compound 5 exhibits a novel mechanism of action inducing cell cycle arrest and apoptosis.
- Further investigation is needed to optimize compound 5 for therapeutic applications, as in vivo studies were negative.