Cucurbitacin E

Names

[ Name ]:
Cucurbitacin E

[Synonym ]:
(9b,10a,16a,23E)-25-(Acetyloxy)-2,16,20-trihydroxy-9-methyl-19-norlanosta-1,5,23-triene-3,11,22-trione
(3E,6R)-6-[(8S,9R,10R,13R,14S,16R,17R)-2,16-Dihydroxy-4,4,9,13,14-pentamethyl-3,11-dioxo-4,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-6-hydroxy-2-methyl-5-oxo-3-hepten-2-ylacetat
19-Norlanosta-1,5,23-triene-3,11,22-trione, 25-(acetyloxy)-2,16,20-trihydroxy-9-methyl-, (9β,10α,16α,23E)-
Acétate de (4R,9β,16α,23E)-2,16,20-trihydroxy-9,10,14-triméthyl-1,11,22-trioxo-4,9-cyclo-9,10-secocholesta-2,5,23-trién-25-yle
α-Elaterin
25-(Acetyloxy)-2b,16a,20-trihydroxy-9b-methyl-19-nor-10a-lanosta-1,5,23E-triene-3,11,22-trione
(3E,6R)-6-[(8S,9R,10R,13R,14S,16R,17R)-2,16-Dihydroxy-4,4,9,13,14-pentamethyl-3,11-dioxo-4,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-6-hydroxy-2-methyl-5-oxo-3-hepten-2-yl acetate
Cucurbitacin E
A-Elaterin
CUCURBITACIN E(SH)
Acétate de (3E,6R)-6-[(8S,9R,10R,13R,14S,16R,17R)-2,16-dihydroxy-4,4,9,13,14-pentaméthyl-3,11-dioxo-4,7,8,9,10,11,12,13,14,15,16,17-dodécahydro-3H-cyclopenta[a]phénanthrén-17-yl]-6-hydroxy-2-méthyl-5-oxo-3-heptèn-2-yle
α-Elaterine
19-Nor-9β,10α-lanosta-1,5,23-triene-3,11,22-trione, 2,16α,20,25-tetrahydroxy-9-methyl-, 25-acetate (8CI)
(4R,9β,16α,23E)-2,16,20-Trihydroxy-9,10,14-trimethyl-1,11,22-trioxo-4,9-cyclo-9,10-secocholesta-2,5,23-trien-25-yl acetate
(4R,9β,16α,23E)-2,16,20-Trihydroxy-9,10,14-trimethyl-1,11,22-trioxo-4,9-cyclo-9,10-secocholesta-2,5,23-trien-25-ylacetat
Estra-1,5-diene-3,11-dione, 17-[(1R,3E)-5-(acetyloxy)-1-hydroxy-1,5-dimethyl-2-oxo-3-hexen-1-yl]-2,16-dihydroxy-4,4,9,14-tetramethyl-, (9β,10α,16α,17β)-
25-acetate
cucurbitacine-e

Biological Activity

[Description]:

Cucurbitacin E is a natural compound which from the climbing stem of Cucumic melo L. Cucurbitacin E significantly suppresses the activity of the cyclin B1/CDC2 complex.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Natural Products >> Terpenoids and Glycosides

Research Areas >> Cancer

[Target]

cyclin B1/CDC2

Autophagy

[In Vitro]

To explore the antitumor activity of Cucurbitacin E (CuE) against colorectal cancer (CRC) cells, an in vitro study is initiated in which each of the CRC cell lines is exposed to increasing doses of Cucurbitacin E (0, 2.5, 5, and 7.5 μM) over a period of 24 h. The proliferation of the Cucurbitacin E-treated cancer cells is then measured using the MTT method. Cucurbitacin E is shown to induce morphological changes in the primary colon cancer cells. Microscopic observation showed that following exposure to Cucurbitacin E (5 μM) between 6 and 24 h, the primary colon cancer cells underwent a remarkable change in morphology. Cucurbitacin E inhibits tumor growth by arresting the cell cycle in the G2/M phase via GADD45γ gene expression and the blockage of cyclin B1/CDC2 complex in primary CRC cells[1].

[In Vivo]

A high fat diet mice model of metabolic syndrome (HFD-MetS) is developed to assess the role of Cucurbitacin E (CuE) on body weight and fat tissue biology. Significant decrease in body weights of HFD-MetS mice treated with Cucurbitacin E (0.5mg/kg) are found as compared to HFD-MetS mice treated with vehicle alone. Cucurbitacin E treatment reduces all fat pads weights in HFD-MetS mice. 55% reduction is observed in total fat in mice, after treatment with Cucurbitacin E in comparison to HFD-MetS mice. Abdominal obesity is strongly associated with metabolic syndrome. Central obesity is reduced to 50% after Cucurbitacin E treatment as compared to HFD MetS mice, elucidating the effectiveness of Cucurbitacin E in targeting MetS[2].

[Cell Assay]

The colorectal cancer (CRC) cells are seeded into 96-well culture plates at 5000 cells/well. The cells are treated with 0, 2.5, 5, and 7.5 μM Cucurbitacin E for 1-3 days. MTT dye (1 mg/mL) is added to each well for at least 4 h of treatment. The reaction is stopped by the addition of DMSO, and optical density is measured at 540 nm on a multi-well plate reader. Background absorbance of the medium in the absence of cells is subtracted. All samples are assayed in triplicate, and the mean for each experiment is calculated. Results are expressed as a percentage of control, which is considered as 100%. Each assay is carried out in triplicate, and the results are expressed as the mean[1].

[Animal admin]

Mice[2] C57BL/6 male mice are used. The mice are designated as metabolic syndrome mice (HFD-MetS-mice). Briefly, the mice are randomly assigned into two groups according to their diet for 8 weeks (n = 10-12): high fat diet group (HFD) (60% fat, 20% carbohydrate, 20% protein) or the matched low fat, standard diet group (SD) (10% fat, 70% carbohydrate, 20% protein). After eight weeks on high fat diet, the mice with significant obese phenotype and fasting blood glucose levels ≥126 mg/dL are considered MetS mice. The MetS mice are continued on the HFD throughout the study. The MetS mice are then randomly divided into three additional groups, according to the treatment administered by oral gavage for 10 weeks (n=10-12): a low dose 0.25 mg/kg/day of Cucurbitacin E designated as HFD+Cucurbitacin E (L) or high dose 0.5 mg/kg/day of Cucurbitacin E, designated as HFD+Cucurbitacin E (H) or 50 mg/kg/day Orlistat (HFD+Orlistat). Animals on SD are administered 0.5% CMC by oral gavage[2].

[References]

[1]. Hsu YC, et al. Therapeutic ROS targeting of GADD45γ in the induction of G2/M arrest in primary human colorectal cancer cell lines by cucurbitacin E. Cell Death Dis. 2014 Apr 24;5:e1198.

[2]. Murtaza M, et al. Cucurbitacin E reduces obesity and related metabolic dysfunction in mice by targeting JAK-STAT5 signaling pathway. PLoS One. 2017 Jun 9;12(6):e0178910.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
712.6±60.0 °C at 760 mmHg

[ Melting Point ]:
228-234ºC

[ Molecular Formula ]:
C₃₂H₄₄O₈

[ Molecular Weight ]:
556.687

[ Flash Point ]:
224.4±26.4 °C

[ Exact Mass ]:
556.303589

[ PSA ]:
138.20000

[ LogP ]:
3.15

[ Vapour Pressure ]:
0.0±5.2 mmHg at 25°C

[ Index of Refraction ]:
1.579

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: RC6305500

CHEMICAL NAME :: 19-Nor-9-beta,10-alpha-lanosta-1,5,23-triene-3,11,22- trione, 2,16-alpha,20,25-tetrahydroxy- 9-methyl-, 25-acetate

CAS REGISTRY NUMBER :: 18444-66-1

BEILSTEIN REFERENCE NO. :: 2343323

LAST UPDATED :: 199612

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C32-H44-O8

MOLECULAR WEIGHT :: 556.76

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 340 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: CHTPBA Chimica Therapeutica. (Paris, France) V.1-8, 1965-73. For publisher information, see EJMCA5. Volume(issue)/page/year: 5,205,1970

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302

[ Hazard Codes ]:
Xn

[ Risk Phrases ]:
25

[ Safety Phrases ]:
1-22-45-24/25

[ RIDADR ]:
UN 3172

[ RTECS ]:
RC6305500

[ HS Code ]:
29153900

Precursor & DownStream

Precursor

DownStream

Articles

Interaction of cucurbitacins with human serum albumin: Thermodynamic characteristics and influence on the binding of site specific ligands.

J. Photochem. Photobiol. B, Biol. 95(3) , 189-95, (2009)

Cucurbitacins (Cuc) are cytotoxic oxygenated triterpenes. Their binding to albumin may control their diffusion and consequently their biological effects. The specific binding site of Cuc to albumin is...

Quantitative determination of cucurbitacin E and cucurbitacin I in homoeopathic mother tincture of Gratiola officinalis L. by HPLC.

Pharmazie 63(12) , 851-3, (2008)

"Hedgehyssop" Gratiola officinalis L. (Scrophulariaceae) is found as an ingredient in homeopathic remedies. Among the active compounds found in G. officinalis, the cucurbitacines constitute a group of...

The induction of G2/M cell-cycle arrest and apoptosis by cucurbitacin E is associated with increased phosphorylation of eIF2alpha in leukemia cells.

Anticancer Drugs 21(4) , 389-400, (2010)

The antiproliferative and apoptotic effects of cucurbitacin E, a natural product isolated from Cucurbitaceae, were determined in human leukemia HL-60 cells. Cucurbitacin E at low concentrations (3-50 ...