Melampodium leucanthum, a source of cytotoxic sesquiterpenes with antimitotic activities

Andrew J. Robles, Jiangnan Peng, Rachel M. Hartley, Brigette Lee, Susan L. Mooberry

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

A new tricyclic sesquiterpene, named meleucanthin (1), was isolated from an extract of the leaves and branches of Melampodium leucanthum, along with four known germacranolide sesquiterpene lactones, leucanthin-A (2), leucanthin-B (3), melampodin-A acetate (4), and 3α-hydroxyenhydrin (5). The chemical structure of 1 was elucidated by analysis of 1D and 2D NMR and mass spectrometric data. All compounds exhibited antiproliferative and cytotoxic efficacy against PC-3 and DU 145 prostate cancer cells, as well as HeLa cervical cancer cells, with IC50 values ranging from 0.18 to 9 μM. These compounds were effective in clonogenic assays and displayed high cellular persistence. They were also found to be capable of circumventing P-glycoprotein-mediated drug resistance. Mechanism of action studies showed that 4 caused an accumulation of cells in the G2/M phase of the cell cycle, and 2-5 caused the formation of abnormal mitotic spindles. These results suggest the cytotoxic effects of these germacranolides involve inhibition of mitotic spindle function, and it is likely that other mechanisms additionally contribute to cell death. These studies also demonstrate the possibility of isolating new, biologically active compounds from indigenous Texas plants.

Original languageEnglish (US)
Pages (from-to)388-395
Number of pages8
JournalJournal of Natural Products
Volume78
Issue number3
DOIs
StatePublished - Mar 27 2015
Externally publishedYes

Fingerprint

Antimitotic Agents
Sesquiterpenes
Spindle Apparatus
Cells
G2 Phase
P-Glycoprotein
Lactones
Drug Resistance
Uterine Cervical Neoplasms
Cell Division
Inhibitory Concentration 50
Prostatic Neoplasms
Cell Cycle
Acetates
Cell Death
Cell death
Assays
Nuclear magnetic resonance
Pharmaceutical Preparations
germacranolide

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Pharmaceutical Science
  • Analytical Chemistry
  • Organic Chemistry
  • Molecular Medicine
  • Complementary and alternative medicine
  • Medicine(all)

Cite this

Melampodium leucanthum, a source of cytotoxic sesquiterpenes with antimitotic activities. / Robles, Andrew J.; Peng, Jiangnan; Hartley, Rachel M.; Lee, Brigette; Mooberry, Susan L.

In: Journal of Natural Products, Vol. 78, No. 3, 27.03.2015, p. 388-395.

Research output: Contribution to journalArticle

Robles, Andrew J. ; Peng, Jiangnan ; Hartley, Rachel M. ; Lee, Brigette ; Mooberry, Susan L. / Melampodium leucanthum, a source of cytotoxic sesquiterpenes with antimitotic activities. In: Journal of Natural Products. 2015 ; Vol. 78, No. 3. pp. 388-395.
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