Disease relevance of Costunolide

• Two active components, costunolide and dehydrocostus lactone, were identified which show strong suppressive effect on the expression of the hepatitis B surface antigen (HBsAg) in human hepatoma Hep3B cells, but have little effect on the viability of the cells [1].
• Furthermore, the suppressive effect of costunolide and dehydrocostus lactone on HBsAg and hepatitis B e antigen (HBeAg), a marker for hepatitis B viral genome replication in human liver cells, was also observed in another human hepatoma cell line HepA2 which was derived from HepG2 cells by transfecting a tandemly repeat hepatitis B virus (HBV) DNA [1].
• In this study we showed that costunolide exerts a dose-dependent antiproliferative activity in the human breast cancer MCF-7 cells [2].
• The minimum inhibitory concentrations (MIC) against Mycobacterium tuberculosis and M. avium of parthenolide, costunolide, 1 (10)-epoxycostunolide and other germacranolide-type sesquiterpene lactones and derivatives were determined by use of a radiorespirometric bioassay [3].

High impact information on Costunolide

• Costunolide decreased four AOM-induced biomarkers, such as the frequencies of ACF/colon, ornithine decarboxylase activity, polyamine concentration level, and silver-stained nucleolar organizer region number in the colon [4].
• Inhibitors for PKC, PI3-K, and ERK markedly inhibited HL-60 cell differentiation induced by costunolide in combination with 1,25-(OH)(2)D(3) [5].
• Potentiation of 1,25-dihydroxyvitamin D(3)-induced differentiation of human promyelocytic leukemia cells into monocytes by costunolide, a germacranolide sesquiterpene lactone [5].
• These results indicate that PKC, PI3-K, ERK and NF-kappaB may be involved in 1,25-(OH)(2)D(3)-mediated cell differentiation enhanced by costunolide [5].
• Costunolide inhibits interleukin-1beta expression by down-regulation of AP-1 and MAPK activity in LPS-stimulated RAW 264.7 cells [6].

Biological context of Costunolide

• Costunolide markedly increased the degree of HL-60 leukemia cell differentiation when simultaneously combined with 5nM 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) [5].
• At 13 weeks of age, the groups exposed to DMBA were fed diet containing PCA or costunolide at a dose of 0.2 g/kg diet (200 ppm) for 17 weeks [7].
• We have previously demonstrated that costunolide, a biologically active compound that was isolated from the stem bark of Magnolia sieboldii, induced apoptosis in human cancer cells [8].
• A sesquiterpene lactone, costunolide, from Magnolia grandiflora inhibits NF-kappa B by targeting I kappa B phosphorylation [9].
• Taken together, these results demonstrate that costunolide inhibits IL-1beta gene expression by blocking the activation of MAPKs and DNA binding of AP-1 in LPS-stimulated RAW 264.7 cells [6].

Anatomical context of Costunolide

• In this report, we investigated the effect of costunolide on cellular differentiation in the human promyelocytic leukemia HL-60 cell culture system [5].
• These results suggest that PCA and costunolide inhibited hamster buccal pouch carcinogenesis and such inhibition may be related to suppression of cell proliferation in the buccal mucosa [7].
• Compound 4d showed around 2-fold better cytotoxicity against SW-620 (colon) cell line with improved safety index than costunolide (1) [10].
• Our data suggest an interaction of costunolide with microtubules, which may represent a new intracellular target for this drug [2].
• While compounds 4e, 4g, and 4p have shown around 2- to 3-fold better cytotoxicity against MIAPaCa2 (pancreas), K-562 (leukemia) and PA-1 (ovary) cell lines as well as better safety index in comparison to costunolide (1) [10].

Associations of Costunolide with other chemical compounds

• The modifying effects of dietary exposure to two natural products, protocatechuic acid (PCA) and costunolide during the development of neoplasms in oral carcinogenesis initiated with 7,12-dimethylbenz[a]anthracene (DMBA) were investigated in male Syrian golden hamsters [7].
• Chemopreventive effect of costunolide, a constituent of oriental medicine, on azoxymethane-induced intestinal carcinogenesis in rats [11].
• In conclusion, the inhibitory effects of costunolide and alpha-MGBL on blood-ethanol elevation were based on inhibition of gastric emptying and dilution of the ethanol concentration by the increased gastric fluid [12].
• Tyrosine phosphorylation induced by crosslinking of CD3 molecules was significantly inhibited by costunolide in a dose-dependent manner [13].
• (1)H, (13)C NMR and X-ray crystallographic studies of highly polyhalogenated derivatives of costunolide lactone [14].

Gene context of Costunolide

• Inhibitory effects of costunolide on the telomerase activity in human breast carcinoma cells [15].
• Costunolide, a sesquiterpene lactone from Saussurea lappa, inhibits the VEGFR KDR/Flk-1 signaling pathway [16].
• In addition, the bindings of transcription factors in hTERT promoters were significantly decreased in both cells by the treatment of costunolide [15].
• Moreover, costunolide inhibited the activity of AP-1 transcription factor, and the phosphorylation of MAPKs, including SAPK/JNK and p38 MAP kinase [6].
• Our data indicate that costunolide induces the ROS-mediated mitochondrial permeability transition and resultant cytochrome c release [17].

Analytical, diagnostic and therapeutic context of Costunolide

• The inhibitory effect of costunolide on AP-1 activity was also confirmed by an electrophoretic mobility shift assay [6].
• PCA or costunolide significantly decreased the tumor burden (P < 0.001-P < 0.05) and the extent of dysplastic areas (%) (P < 0.001-P < 0.05) [7].
• Northern blotting analysis shows that the suppression of HBsAg gene expression by both costunolide and dehydrocostus lactone were mainly at the mRNA level [1].

References