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.
authors.affiliation: Department of Pharmacology and ‡Cancer Therapy & Research Center, The University of Texas Health Science Center at San Antonio , San Antonio, Texas 78229, United States.|Department of Chemistry and Biochemistry, ⊥Natural Products Discovery Group, and ∥Institute for Natural Products Applications and Research Technologies, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Corena V
authors.initials: CV
authors.lastname: Shaffer
authors.affiliation: Department of Pharmacology and ‡Cancer Therapy & Research Center, The University of Texas Health Science Center at San Antonio , San Antonio, Texas 78229, United States.|Department of Chemistry and Biochemistry, ⊥Natural Products Discovery Group, and ∥Institute for Natural Products Applications and Research Technologies, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Shengxin
authors.initials: S
authors.lastname: Cai
authors.affiliation: Department of Pharmacology and ‡Cancer Therapy & Research Center, The University of Texas Health Science Center at San Antonio , San Antonio, Texas 78229, United States.|Department of Chemistry and Biochemistry, ⊥Natural Products Discovery Group, and ∥Institute for Natural Products Applications and Research Technologies, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Jiangnan
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Pharmacology and ‡Cancer Therapy & Research Center, The University of Texas Health Science Center at San Antonio , San Antonio, Texas 78229, United States.|Department of Chemistry and Biochemistry, ⊥Natural Products Discovery Group, and ∥Institute for Natural Products Applications and Research Technologies, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Robles
authors.affiliation: Department of Pharmacology and ‡Cancer Therapy & Research Center, The University of Texas Health Science Center at San Antonio , San Antonio, Texas 78229, United States.|Department of Chemistry and Biochemistry, ⊥Natural Products Discovery Group, and ∥Institute for Natural Products Applications and Research Technologies, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Hartley
authors.affiliation: Department of Pharmacology and ‡Cancer Therapy & Research Center, The University of Texas Health Science Center at San Antonio , San Antonio, Texas 78229, United States.|Department of Chemistry and Biochemistry, ⊥Natural Products Discovery Group, and ∥Institute for Natural Products Applications and Research Technologies, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Powell
authors.affiliation: Department of Pharmacology and ‡Cancer Therapy & Research Center, The University of Texas Health Science Center at San Antonio , San Antonio, Texas 78229, United States.|Department of Chemistry and Biochemistry, ⊥Natural Products Discovery Group, and ∥Institute for Natural Products Applications and Research Technologies, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Lin
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Pharmacology and ‡Cancer Therapy & Research Center, The University of Texas Health Science Center at San Antonio , San Antonio, Texas 78229, United States.|Department of Chemistry and Biochemistry, ⊥Natural Products Discovery Group, and ∥Institute for Natural Products Applications and Research Technologies, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Cichewicz
authors.affiliation: Department of Pharmacology and ‡Cancer Therapy & Research Center, The University of Texas Health Science Center at San Antonio , San Antonio, Texas 78229, United States.|Department of Chemistry and Biochemistry, ⊥Natural Products Discovery Group, and ∥Institute for Natural Products Applications and Research Technologies, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Mooberry
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D047188:Chalcones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D045788:Sesquiterpenes, Germacrane / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013781:Texas; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D012717:Sesquiterpenes; D045788:Sesquiterpenes, Germacrane; D014404:Tubulin; D050257:Tubulin Modulators