Texas Native Plants Yield Compounds with Cytotoxic Activities against Prostate Cancer Cells

Corena V. Shaffer, Shengxin Cai, Jiangnan Peng, Andrew J. Robles, Rachel M. Hartley, Douglas R. Powell, Lin Du, Robert H. Cichewicz, Susan L. Mooberry

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

There remains a critical need for more effective therapies for the treatment of late-stage and metastatic prostate cancers. Three Texas native plants yielded three new and three known compounds with antiproliferative and cytotoxic activities against prostate cancer cells with IC50 values in the range of 1.7-35.0 μM. A new sesquiterpene named espadalide (1), isolated from Gochnatia hypoleuca, had low micromolar potency and was highly effective in clonogenic assays. Two known bioactive germacranolides (2 and 3) were additionally isolated from G. hypoleuca. Dalea frutescens yielded two new isoprenylated chalcones, named sanjuanolide (4) and sanjoseolide (5), and the known sesquiterpenediol verbesindiol (6) was isolated from Verbesina virginica. Mechanistic studies showed that 1-4 caused G2/M accumulation and the formation of abnormal mitotic spindles. Tubulin polymerization assays revealed that 4 increased the initial rate of tubulin polymerization, but did not change total tubulin polymer levels, and 1-3 had no effects on tubulin polymerization. Despite its cytotoxic activity, compound 6 did not initiate changes in cell cycle distribution and has a mechanism of action different from the other compounds. This study demonstrates that new compounds with significant biological activities germane to unmet oncological needs can be isolated from Texas native plants.

Original languageEnglish (US)
Pages (from-to)531-540
Number of pages10
JournalJournal of Natural Products
Volume79
Issue number3
DOIs
StatePublished - Mar 25 2016

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Texas Native Plants Yield Compounds with Cytotoxic Activities against Prostate Cancer Cells'. Together they form a unique fingerprint.

  • Cite this

    Shaffer, C. V., Cai, S., Peng, J., Robles, A. J., Hartley, R. M., Powell, D. R., Du, L., Cichewicz, R. H., & Mooberry, S. L. (2016). Texas Native Plants Yield Compounds with Cytotoxic Activities against Prostate Cancer Cells. Journal of Natural Products, 79(3), 531-540. https://doi.org/10.1021/acs.jnatprod.5b00908