Cucurbitacin I

InvivoChem Cat #:V4972CAS #:2222-07-3Purity >=98%

Description: Cucurbitacin I, a naturally occurring triterpene analog, is a novel, potent and selective inhibitor of JAK2/STAT3 with potent anti-cancer activity on a variety of cancer cell types. autophagy and apoptosis were induced by cucurbitacin I. Exposure of GBM (glioblastoma multiform) cells to cucurbitacin I resulted in pronounced apoptotic cell death through activating bcl-2 family proteins. Cells treatment with cucurbitacin I up-regulated Beclin 1 and triggered autophagosome formation and accumulation as well as conversion of LC3I to LC3II. Activation of the AMP-activated protein kinase/mammalian target of rapamycin/p70S6K pathway, but not the PI3K/AKT pathway, occurred in autophagy induced by cucurbitacin I, which was accompanied by decreased hypoxia-inducible factor 1alpha. Stable overexpression of hypoxia-inducible factor 1alpha induced by FG-4497 prevented cucurbitacin I-induced autophagy and down-regulation of bcl-2. Knockdown of beclin 1 or treatment with the autophagy inhibitor 3-methyladenine also inhibited autophagy induced by cucurbitacin I. A coimmunoprecipitation assay showed that the interaction of Bcl-2 and Beclin 1/hVps34 decreased markedly in cells treated with cucurbitacin I. Furthermore, knockdown of beclin 1 or treatment with the lysosome inhibitor chloroquine sensitized cancer cells to cucurbitacin I-induced apoptosis. Finally, a xenograft model provided additional evidence for the occurrence of cucurbitacin I-induced apoptosis and autophagy in vitro. These findings provide new insights into the molecular mechanisms underlying cucurbitacin I-mediated GBM cell death and may provide an efficacious therapy for patients harboring GBM.

References: J Biol Chem. 2014 Apr 11; 289(15):10607-19; J Invest Dermatol. 2008 Jul; 128(7):1691-5.

Related CAS #: 2222-07-3 (Cucurbitacin I); 18444-66-1 (Cucurbitacin E); 6199-67-3 (Cucurbitacin B); 50298-90-3 (Cucurbitacin IIb); 3877-86-9 (Cucurbitacin D); 58546-34-2 (Cucurbitacin IIa; Hemslecin A)

-20C for 3 years in powder form

Synonym: Cucurbitacin I; Elatericin B; JSI-124; JSI 124; JSI124; NSC 521777; NSC-521777; NSC521777;
IUPAC/Chemical Name: (8S, 9R, 10R, 13R, 14S, 16R, 17R)-17-[(E, 2R)-2, 6-dihydroxy-6-methyl-3-oxohept-4-en-2-yl]-2, 16-dihydroxy-4, 4, 9, 13, 14-pentamethyl-8, 10, 12, 15, 16, 17-hexahydro-7H-cyclopenta[a]phenanthrene-3, 11-dione
InChi Key: NISPVUDLMHQFRQ-MKIKIEMVSA-N
InChi Code: InChI=1S/C30H42O7/c1-25(2, 36)12-11-21(33)30(8, 37)23-19(32)14-27(5)20-10-9-16-17(13-18(31)24(35)26(16, 3)4)29(20, 7)22(34)15-28(23, 27)6/h9, 11-13, 17, 19-20, 23, 31-32, 36-37H, 10, 14-15H2, 1-8H3/b12-11+/t17-, 19-, 20+, 23+, 27+, 28-, 29+, 30+/m1/s1
SMILES Code: O=C(C(C)(C)C1=CC[C]2([H])[C]3(C)C[CH](O)[CH]([C](C(/C=C/C(C)(O)C)=O)(O)C)[C]3(C)C4)C(O)=C[C]1([H])