Journal: Breast Cancer Research : BCR

Article Title: Parthenolide and costunolide reduce microtentacles and tumor cell attachment by selectively targeting detyrosinated tubulin independent from NF-κB inhibition

doi: 10.1186/bcr3477

Figure Lengend Snippet: Parthenolide and costunolide decrease detyrosinated tubulin in human breast carcinoma cells. (A) Bt‒549 (N = 3) and MDA‒MB‒157 (N = 6) cells treated for six hours with DMSO (Veh; 0.1%), parthenolide (Parth; 5 μM, 10 μM, 25 μM), costunolide (Cost; 5 μM, 10 μM, 25 μM), resveratrol (ResV; 50 μg/ml), colchicine (Col; 50 μM), and Taxol (Tax; 0.5 μg/ml). Parthenolide (10 μM, 25 μM), costunolide (10 μM, 25 μM), and colchicine (50 μM) significantly reduced detyrosinated tubulin (Detyr) levels compared to vehicle (*P <0.05; ** P <0.001, t‒test). Resveratrol, a non‒sesquiterpene lactone NF‒κB inhibitor, did not significantly affect detyrosinated tubulin (P >0.5, t‒test). Taxol significantly increased detyrosinated tubulin (‡Bt‒549 Tax value is × 2.5; MDA‒MB‒157 Tax value is × 10). None of the compounds induced apoptosis in these cells, as gauged by PARP cleavage. Columns, mean densitometry for N = 3 (Bt‒549) or N = 6 (MDA‒MB‒157) experiments; bars, SD. (B) Comparison of the compounds used show parthenolide and costunolide, two sesquiterpene lactones, are structurally similar while the other compounds are structurally dissimilar. DMSO, dimethyl sulfoxide; NF-κB, nuclear factor-kappaB; PARP, poly(ADP-ribose) polymerase.

Article Snippet: Costunolide (Cost) was purchased from Chromadex (Santa Ana, CA, USA).

Techniques: Comparison

Journal: Breast Cancer Research : BCR

Article Title: Parthenolide and costunolide reduce microtentacles and tumor cell attachment by selectively targeting detyrosinated tubulin independent from NF-κB inhibition

doi: 10.1186/bcr3477

Figure Lengend Snippet: Parthenolide and costunolide decrease detyrosinated tubulin without compromising the overall microtubule network. Immunofluorescence of six-hour drug treated (A) Bt-549 and (B) MDA-MB-157 stained for detyrosinated tubulin and α-tubulin show that parthenolide (Parth; 10 μM) and costunolide (Cost; 25 μM) decrease and disrupt filamentous detyrosinated tubulin (Detyr) while leaving the overall microtubule network intact (α-tub). Treatment with colchicine (Col; 50 μM) disrupts both detyrosinated and α-tubulin filaments. Taxol (Tax; 0.5 μg/ml) increases bundling and disrupts organization of detyrosinated and α-tubulin filaments. Resveratrol (ResV; 50 μg/ml) did not significantly affect detyrosinated or α-tubulin.

Article Snippet: Costunolide (Cost) was purchased from Chromadex (Santa Ana, CA, USA).

Techniques: Immunofluorescence, Staining

Journal: Breast Cancer Research : BCR

Article Title: Parthenolide and costunolide reduce microtentacles and tumor cell attachment by selectively targeting detyrosinated tubulin independent from NF-κB inhibition

doi: 10.1186/bcr3477

Figure Lengend Snippet: Parthenolide and costunolide decrease microtentacle (McTN) frequency and attachment. (A) Detached Bt-549 and MDA-MB-157 were pretreated for six hours and suspended in drug-containing media for blind McTN scoring. Parthenolide (Parth; 10 μM), costunolide (Cost; 25 μM), and colchicine (Col; 50 μM) show a significant decrease compared to vehicle treated (* P <0.05; ** P <0.001, t-test). Resveratrol (ResV; 50 μg/ml) and Taxol (Tax; 0.5 μg/ml) did not have a significant effect on McTN frequency. Columns, mean %McTNs for six independent experiments in which at least 100 cells were scored blindly; bars, SD. (B) Live population images of suspended Bt-549 and MDA-MB-157. McTNs are observed in vehicle, resveratrol, and Taxol (black arrows).

Article Snippet: Costunolide (Cost) was purchased from Chromadex (Santa Ana, CA, USA).

Techniques:

Journal: The Journal of Biological Chemistry

Article Title: Lettuce Costunolide Synthase ( CYP71BL2 ) and Its Homolog ( CYP71BL1 ) from Sunflower Catalyze Distinct Regio- and Stereoselective Hydroxylations in Sesquiterpene Lactone Metabolism *

doi: 10.1074/jbc.M110.216804

Figure Lengend Snippet: Costunolide biosynthetic pathway in Asteraceae. COS, costunolide synthase.

Article Snippet: The authentic costunolide standard was purchased from AvaChem Scientific (San Antonio, TX).

Techniques:

Journal: The Journal of Biological Chemistry

Article Title: Lettuce Costunolide Synthase ( CYP71BL2 ) and Its Homolog ( CYP71BL1 ) from Sunflower Catalyze Distinct Regio- and Stereoselective Hydroxylations in Sesquiterpene Lactone Metabolism *

doi: 10.1074/jbc.M110.216804

Figure Lengend Snippet: Biochemical and chemical characterizations of germacrene A acid 8β-hydroxylase. A and B, (±)LC-MS analyses of C12 (HaG8H) enzymatic products are shown. Microsomes from the yeast expressing C12 and CPR catalyzes the synthesis of a new compound (labeled as 3) with [M-H2O+H]+ ion at m/z 233 in A and with [M-H]− ion at m/z 249 in B. The 6-hydroxy-GAA (compound 2) was prepared by alkaline hydrolysis of authentic costunolide standard (1). The identity of 2 was confirmed by reverting it to costunolide. The chemical identity of the peak marked by asterisk is unknown. The compound marked by the star in A (inset) is a minor compound displaying m/z 233, but it showed different retention time from the costunolide (8.03 min versus 7.66 min). C, structures of the new compound (3) purified from the in vivo feeding assay (8β-hydroxygermacrene A acid) and its rearranged product in an acidic condition (8β-hydroxyilicic acid). In the 8β-hydroxyilicic acid, the stereochemistry of a C15 methyl and a hydroxyl group attached to C4 could not be determined due to NMR signal overlapping.

Article Snippet: The authentic costunolide standard was purchased from AvaChem Scientific (San Antonio, TX).

Techniques: Liquid Chromatography with Mass Spectroscopy, Expressing, Labeling, Purification, In Vivo, Feeding Assay

Journal: The Journal of Biological Chemistry

Article Title: Lettuce Costunolide Synthase ( CYP71BL2 ) and Its Homolog ( CYP71BL1 ) from Sunflower Catalyze Distinct Regio- and Stereoselective Hydroxylations in Sesquiterpene Lactone Metabolism *

doi: 10.1074/jbc.M110.216804

Figure Lengend Snippet: Biochemical and chemical characterization of costunolide synthase. A, (+)LC-MS scan at m/z 233 demonstrated that compounds 1 and 2 showed identical retention times with costunolide and 6-hydroxygermacrene A acid, respectively. Asterisks indicate unknown compounds, which are likely due to the unspecific activities of LsCOS. B, the structures of the standards are depicted. C, metabolite profile of the culture extraction from the EPY300 strain expressing GAS, LsGAO, CPR, and with or without LsCOS by (+)LC-MS scan at m/z 233. D, product ion scans of the costunolide standard and compound 1 by (+)LC-MS-MS showed identical fragmenting patterns. Diamonds indicate the parental ion at m/z 233.

Article Snippet: The authentic costunolide standard was purchased from AvaChem Scientific (San Antonio, TX).

Techniques: Liquid Chromatography with Mass Spectroscopy, Extraction, Expressing

Journal: Biology

Article Title: Tongqiaohuoxue Hinders Development and Progression of Atherosclerosis: A Possible Role in Alzheimer’s Disease

doi: 10.3390/biology9110363

Figure Lengend Snippet: HPLC chromatograms of the standard mixture ( A ) and THD sample ( B ) at UV detection wavelengths of 214 nm ( I ), 220 nm ( II ), 230 nm ( III ), 270 nm ( IV ), 280 nm ( V ), 320 nm ( VI ), and 400 nm ( VII ). Gallic acid (1), amygdalin (2), albiflorin (3), paeoniflorin (4), ferulic acid (5), safflomin A (6), benzoic acid (7), benzoylpaeoniflorin (8), 6-gingerol (9), costunolide (10), and dehydrocostus lactone (11).

Article Snippet: We used 11 standard reference compounds for quality assessment of THD—gallic acid (99.5%), amygdalin (99.0%), albiflorin (99.8%), paeoniflorin (99.4%), ferulic acid (98.0%), safflomin A (99.7%), benzoic acid (99.9%), benzoylpaeoniflorin (98.0%), 6-gingerol (99.3%), costunolide (98.0%), and dehydrocostus lactone (98.0%) (Merck KGaA, Darmstadt, Germany; Wako Chemicals, Osaka, Japan; Chem Faces Biochemical Co., Ltd., Wuhan, China; Shanghai Sunny Biotech Co., Ltd., Shanghai, China).

Techniques:

Journal: Biomolecules & Therapeutics

Article Title: Unraveling Stereochemical Structure-Activity Relationships of Sesquiterpene Lactones for Inhibitory Effects on STAT3 Activation

doi: 10.4062/biomolther.2023.210

Figure Lengend Snippet: Protein-ligand docking study of sesquiterpene lactones in STAT3. (A) Domain structured of STAT3. SH2, Src homology 2; TAD, transactivation domain. (B) X-ray crystal structure of p-STAT3 homodimer. (C) Key interacting amino acid residues of pTyr705 in SH2 domain binding pocket. Hydrogen bonds were shown in black dashes. (D) The location of SH2 domain binding pocket. Selected docking poses of sesquiterpene lactones; (E) alantolactone, (F) isoalantolactone, (G) parthenolide, (H) costunolide, (I) atractylenoide I, and (J) sclareolide. Top ten most energy-minimized binding modes of (K) dehydrocostus lactone, and (L) tulipalin A were compared with those of alantolactone.

Article Snippet: Alantolactone, isoalantolactone, costunolide, dehydrocostus lactone, parthenolide, atractylenolide I, atractylenolide II, atractylenolide III, and sclareolide, were purchased from Tauto Biotech (Shanghai, China).

Techniques: Binding Assay

Journal: Cancer Letters

Article Title: Bcl-X L , but not Bcl-2, can protect human B-lymphoma cell lines from parthenolide-induced apoptosis

doi: 10.1016/j.canlet.2011.11.035

Figure Lengend Snippet: Parthenolide induced apoptosis in a dose-dependent and time-dependent manner in some, but not all, B-lymphoma cell lines. (A) SUDHL-4 or RC-K8 cells were treated with parthenolide (PN) for 6 h at the indicated concentrations, and extracts were assessed for DNA laddering (top panel), caspase-3 activity (middle panel), and PARP cleavage (bottom panel). Anti-NF-κB p65 Western blotting was performed as a loading control. (B) SUDHL-4 or RC-K8 cells were treated with parthenolide (PN) for 6 h with 25 μM parthenolide for the indicated times. β-tubulin Western blotting was performed as a loading control. (C) SUDHL-4 or RC-K8 cells were treated for 6 h with vehicle (DMSO), 50 μM costunolide (CT), 25 μM parthenolide (PN) or 50 μM helenalin (HL). PARP cleavage was detected by Western blotting.

Article Snippet: Twenty-four hours prior to treatment with parthenolide (Fermentek, Jerusalem, Israel), helenalin (ChromaDex, Irvine, CA, USA) or costunolide (AvaChem Scientific, San Antonio, TX, USA), cells were plated into 60-mm or 35-mm plates at approximately 60–70% confluency.

Techniques: DNA Laddering, Activity Assay, Western Blot, Control

Journal: Plants

Article Title: Targeted Screening and Quantification of Characteristic Sesquiterpene Lactones in Ambrosia artemisiifolia L. at Different Growth Stages

doi: 10.3390/plants13152053

Figure Lengend Snippet: Characteristics of the calibration curves and limit of detection and quantification values, and results of the system suitability test. (LOD: limit of detection, LOQ: limit of quantification, RSD: relative standard deviation, RT: retention time).

Article Snippet: The sesquiterpene lactones psilostachyin ( 1 ), peruvin ( 2 ), and acetoxydihydrodamsin ( 3 ) were isolated by our group [ ]; costunolide ( 4 ) was obtained from Merck KGaA (Darmstadt, Germany; purity >97%), while isoalantolactone ( 5 ) was purchased from MedChemExpress LLC (Monmouth Junction, NJ, USA; purity 99.99%).

Techniques: Standard Deviation

Journal: Plants

Article Title: Targeted Screening and Quantification of Characteristic Sesquiterpene Lactones in Ambrosia artemisiifolia L. at Different Growth Stages

doi: 10.3390/plants13152053

Figure Lengend Snippet: Contents of marker compounds in aerial parts of A. artemisiifolia collected near Szeged, Hungary.

Article Snippet: The sesquiterpene lactones psilostachyin ( 1 ), peruvin ( 2 ), and acetoxydihydrodamsin ( 3 ) were isolated by our group [ ]; costunolide ( 4 ) was obtained from Merck KGaA (Darmstadt, Germany; purity >97%), while isoalantolactone ( 5 ) was purchased from MedChemExpress LLC (Monmouth Junction, NJ, USA; purity 99.99%).

Techniques: Marker

Journal: Plants

Article Title: Targeted Screening and Quantification of Characteristic Sesquiterpene Lactones in Ambrosia artemisiifolia L. at Different Growth Stages

doi: 10.3390/plants13152053

Figure Lengend Snippet: Contents of marker compounds in aerial parts of A. artemisiifolia collected near Nyíri, Hungary.

Article Snippet: The sesquiterpene lactones psilostachyin ( 1 ), peruvin ( 2 ), and acetoxydihydrodamsin ( 3 ) were isolated by our group [ ]; costunolide ( 4 ) was obtained from Merck KGaA (Darmstadt, Germany; purity >97%), while isoalantolactone ( 5 ) was purchased from MedChemExpress LLC (Monmouth Junction, NJ, USA; purity 99.99%).

Techniques: Marker

Journal: Plants

Article Title: Targeted Screening and Quantification of Characteristic Sesquiterpene Lactones in Ambrosia artemisiifolia L. at Different Growth Stages

doi: 10.3390/plants13152053

Figure Lengend Snippet: Correlation data between climatic factors and concentration levels of sesquiterpene lactones.

Article Snippet: The sesquiterpene lactones psilostachyin ( 1 ), peruvin ( 2 ), and acetoxydihydrodamsin ( 3 ) were isolated by our group [ ]; costunolide ( 4 ) was obtained from Merck KGaA (Darmstadt, Germany; purity >97%), while isoalantolactone ( 5 ) was purchased from MedChemExpress LLC (Monmouth Junction, NJ, USA; purity 99.99%).

Techniques: Concentration Assay

Journal: Molecules

Article Title: Sesquiterpene Lactones Containing an α-Methylene-γ-Lactone Moiety Selectively Down-Regulate the Expression of Tumor Necrosis Factor Receptor 1 by Promoting Its Ectodomain Shedding in Human Lung Adenocarcinoma A549 Cells

doi: 10.3390/molecules29081866

Figure Lengend Snippet: Parthenolide and costunolide promoted TNF-R1 shedding in A549 cells. ( A ) Structures of parthenolide and costunolide. ( B – G ) A549 cells were treated with parthenolide ( B – D ) and costunolide ( E – G ) for 1 h at the concentrations indicated in the figure panels. Blots are representative of three independent experiments ( B , E ). The amount of TNF-R1 protein was normalized to the amount of β-actin. The levels of soluble TNF-R1 protein (fold) in the culture medium ( C , F ) and TNF-R1 protein (%) in the cell lysates ( D , G ) are shown as the mean ± standard error of three independent experiments. * p < 0.05 and ** p < 0.01. Original blots are shown in .

Article Snippet: Alantolactone (catalog number: S8318; Selleck Chemicals, Houston, TX, USA), bafilomycin A 1 (item number: 119038; Cayman Chemical, Ann Arbor, MI, USA), costunolide (product number: 032-13731; Wako Pure Chemical Industries, Osaka, Japan), glutathione (product number: 073-02013; FUJIFILM Wako Pure Chemical Corporation, Osaka, Japan), L-cysteine (product number: 10309-41: Nacalai Tesque), Z-Leu-Leu-Leu-H (aldehyde) (also known as MG-132) (code number: 3175-v; Peptide Institute, Osaka, Japan), NAC (product number: 00512-84; Nacalai Tesque), parthenolide (catalog number: P0667-5MG; Sigma, St. Louis, MO, USA), and TAPI-2 (code number: INH-3852-PI; Peptide Institute) were purchased as commercial products. (11 S )-2α-bromo-3-oxoeudesmano-12,6α-lactone (also known as santonin-related compound 2: SRC2) ( 1 ), (11 S )-3-oxoeudesmano-12,6α-lactone ( 2 ), 2α-bromo-3-oxoeudesm-11(13)-eno-12,6α-lactone ( 3 ), 3-oxoeudesm-11(13)-eno-12,6α-lactone ( 4 ), (11 S )-3-oxoeudesm-1-eno-12,6α-lactone ( 5 ), (11 S )-3β-hydroxyeudesm-1-eno-12,6α-lactone ( 6 ), 3-oxoeudesma-1,11(13)-dieno-12,6α-lactone (also known as (+)-tuberiferin) ( 7 ), and 3β-hydroxyeudesma-1,11(13)-dieno-12,6α-lactone ( 8 ) were synthesized as previously described [ , , ].

Techniques: