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

9 Citations (Scopus)

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

Fingerprint

Tubulin
Prostatic Neoplasms
Cells
Polymerization
Verbesina
Assays
Chalcones
Spindle Apparatus
Sesquiterpenes
Bioactivity
Inhibitory Concentration 50
Cell Cycle
Polymers
Therapeutics

ASJC Scopus subject areas

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

Cite this

Shaffer, C. V., Cai, S., Peng, J., Robles, A. J., Hartley, R. M., Powell, D. R., ... 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

Texas Native Plants Yield Compounds with Cytotoxic Activities against Prostate Cancer Cells. / Shaffer, Corena V.; Cai, Shengxin; Peng, Jiangnan; Robles, Andrew J.; Hartley, Rachel M.; Powell, Douglas R.; Du, Lin; Cichewicz, Robert H.; Mooberry, Susan L.

In: Journal of Natural Products, Vol. 79, No. 3, 25.03.2016, p. 531-540.

Research output: Contribution to journalArticle

Shaffer, CV, Cai, S, Peng, J, Robles, AJ, Hartley, RM, Powell, DR, Du, L, Cichewicz, RH & Mooberry, SL 2016, 'Texas Native Plants Yield Compounds with Cytotoxic Activities against Prostate Cancer Cells', Journal of Natural Products, vol. 79, no. 3, pp. 531-540. https://doi.org/10.1021/acs.jnatprod.5b00908
Shaffer, Corena V. ; Cai, Shengxin ; Peng, Jiangnan ; Robles, Andrew J. ; Hartley, Rachel M. ; Powell, Douglas R. ; Du, Lin ; Cichewicz, Robert H. ; Mooberry, Susan L. / Texas Native Plants Yield Compounds with Cytotoxic Activities against Prostate Cancer Cells. In: Journal of Natural Products. 2016 ; Vol. 79, No. 3. pp. 531-540.
@article{cc701c0ba6e7493cb13d41e0afc6b14e,
title = "Texas Native Plants Yield Compounds with Cytotoxic Activities against Prostate Cancer Cells",
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.",
author = "Shaffer, {Corena V.} and Shengxin Cai and Jiangnan Peng and Robles, {Andrew J.} and Hartley, {Rachel M.} and Powell, {Douglas R.} and Lin Du and Cichewicz, {Robert H.} and Mooberry, {Susan L.}",
year = "2016",
month = "3",
day = "25",
doi = "10.1021/acs.jnatprod.5b00908",
language = "English (US)",
volume = "79",
pages = "531--540",
journal = "Journal of Natural Products",
issn = "0163-3864",
publisher = "American Chemical Society",
number = "3",

}

TY - JOUR

T1 - Texas Native Plants Yield Compounds with Cytotoxic Activities against Prostate Cancer Cells

AU - Shaffer, Corena V.

AU - Cai, Shengxin

AU - Peng, Jiangnan

AU - Robles, Andrew J.

AU - Hartley, Rachel M.

AU - Powell, Douglas R.

AU - Du, Lin

AU - Cichewicz, Robert H.

AU - Mooberry, Susan L.

PY - 2016/3/25

Y1 - 2016/3/25

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84962376934&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962376934&partnerID=8YFLogxK

U2 - 10.1021/acs.jnatprod.5b00908

DO - 10.1021/acs.jnatprod.5b00908

M3 - Article

C2 - 26785306

AN - SCOPUS:84962376934

VL - 79

SP - 531

EP - 540

JO - Journal of Natural Products

JF - Journal of Natural Products

SN - 0163-3864

IS - 3

ER -