Cucurbitacin B

Names

[ Name ]:
Cucurbitacin B

[Synonym ]:
19-Nor-9β,10α-lanosta-5,23-diene-3,11,22-trione, 2β,16α,20,25-tetrahydroxy-9-methyl-, 25-acetate
(2S,4R,9β,16α,23E)-2,16,20-Trihydroxy-9,10,14-trimethyl-1,11,22-trioxo-4,9-cyclo-9,10-secocholesta-5,23-dien-25-yl acetate
(2b,9b,10a,16a,23E)-25-(Acetyloxy)-2,16,20-trihydroxy-9-methyl-19-norlanosta-5,23-diene-3,11,22-trione
1,2-Dihydro-a-elaterin
19-Norlanosta-5,23-diene-3,11,22-trione, 25-(acetyloxy)-2,16,20-trihydroxy-9-methyl-, (2β,9β,10α,16α,23E)-
Cucurbitacin B hydrate
19-nor-9β,10α-Lanosta-5,23-diene-3,11,22-trione, 9-methyl-2β,16α,20,25-tetrahydroxy-, 25-acetate
Estr-5-ene-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-, (2β,9β,10α,16α,17β)-
1,2-Dihydro-α-elaterin
[(E,6R)-6-[(2S,8S,9R,10R,13R,14S,16R,17R)-2,16-dihydroxy-4,4,9,13,14-pentamethyl-3,11-dioxo-2,7,8,10,12,15,16,17-octahydro-1H-cyclopenta[a]phenanthren-17-yl]-6-hydroxy-2-methyl-5-oxohept-3-en-2-yl] acetate
25-(Acetyloxy)-2b,16a,20-trihydroxy-9b-methyl-19-nor-10a-lanosta-5,23E-diene-3,11,22-trione

Biological Activity

[Description]:

Cucurbitacin B belongs to a class of highly oxidized tetracyclic triterpenoids; could repress cancer cell progression.IC50 value:Target: anticancer natural compoundin vitro: Cucurbitacin-B inhibited growth and modulated expression of cell-cycle regulators in SHSY5Y cells. At the molecular level, we found that Cucurbitacin-B inhibited AKT signaling activation through up-regulation of PTEN [1]. CuB induced apoptosis of A549 cells in a -concentration-dependent manner, as determined by fluorescence microscopy, flow cytometry and transmission electron microscopy. CuB dose-dependently inhibited lung cancer cell proliferation, with cell cycle inhibition and cyclin B1 downregulation. Apoptosis induced by CuB was shown to be associated with cytochrome c release, B-cell lymphoma 2 downregulation and signal transducer and activator of transcription 3 pathway inhibition [2]. CuB inhibited ITGA6 and ITGB4 (integrin α6 and integrin β4), which are overexpressed in breast cancer. Furthermore, CuB also induced the expression of major ITGB1and ITGB3, which are known to cause integrin-mediated cell death [3]. Cuc B treatment caused DNA double-strand breaks (DSBs) without affecting the signal transducer and activator of transcription 3 (STAT3), the potential molecular target for Cuc B. Cuc B triggers ATM-activated Chk1-Cdc25C-Cdk1, which could be reversed by both ATM siRNA and Chk1 siRNA. Cuc B also triggers ATM-activated p53-14-3-3-σ pathways, which could be reversed by ATM siRNA [4].in vivo: Efficacy of CuB was tested in vivo using two different orthotopic models of breast cancer. MDA-MB-231 and 4T-1 cells were injected orthotopically in the mammary fat pad of female athymic nude mice or BALB/c mice respectively. Our results showed that CuB administration inhibited MDA-MB-231 orthotopic tumors by 55%, and 4T-1 tumors by 40%. The 4T-1 cells represent stage IV breast cancer and form very aggressive tumors [3].

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Cytoskeleton >> Integrin

Research Areas >> Cancer

Natural Products >> Terpenoids and Glycosides

[References]

[1]. Shang Y, et al. Cucurbitacin-B inhibits neuroblastoma cell proliferation through up-regulation of PTEN. Eur Rev Med Pharmacol Sci. 2014;18(21):3297-303.

[2]. Zhang M, et al. Cucurbitacin B inhibits proliferation and induces apoptosis via STAT3 pathway inhibition in A549 lung cancer cells. Mol Med Rep. 2014 Dec;10(6):2905-11.

[3]. Gupta P, et al. Inhibition of Integrin-HER2 signaling by Cucurbitacin B leads to in vitro and in vivo breast tumor growth suppression. Oncotarget. 2014 Apr 15;5(7):1812-28.

[4]. Guo J, et al. Cucurbitacin B induced ATM-mediated DNA damage causes G2/M cell cycle arrest in a ROS-dependent manner. PLoS One. 2014 Feb 4;9(2):e88140.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
699.3±55.0 °C at 760 mmHg

[ Melting Point ]:
184-186ºC

[ Molecular Formula ]:
C₃₂H₄₆O₈

[ Molecular Weight ]:
558.703

[ Flash Point ]:
218.8±25.0 °C

[ Exact Mass ]:
558.319275

[ PSA ]:
138.20000

[ LogP ]:
2.31

[ Vapour Pressure ]:
0.0±5.0 mmHg at 25°C

[ Index of Refraction ]:
1.568

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: RC6190000

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

CAS REGISTRY NUMBER :: 6199-67-3

LAST UPDATED :: 199801

DATA ITEMS CITED :: 3

MOLECULAR FORMULA :: C32-H46-O8

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 :: 14 mg/kg

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

REFERENCE :: CTYAD8 Zhongcaoyao. Chinese Traditional and Herbal Medicine. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.11- 1980- Volume(issue)/page/year: 23,605,1992

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1 mg/kg

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

REFERENCE :: CTYAD8 Zhongcaoyao. Chinese Traditional and Herbal Medicine. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.11- 1980- Volume(issue)/page/year: 23,605,1992

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

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 2730 ug/kg

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

REFERENCE :: CTYAD8 Zhongcaoyao. Chinese Traditional and Herbal Medicine. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.11- 1980- Volume(issue)/page/year: 23,605,1992

Safety Information

[ Hazard Codes ]:
T

[ Risk Phrases ]:
25

[ Safety Phrases ]:
45-24/25

[ RIDADR ]:
UN 2811 6.1 / PGI

[ RTECS ]:
RC6190000

[ Packaging Group ]:
II