Cytotoxic Activity of Some Natural and Synthetic Sesquiterpene Lactones

Bruno, Maurizio; Rosselli, Sergio; Maggio, Antonella; Raccuglia, Rosa Angela; Bastow, Kenneth F.; Wu, Chin Chung; Lee, Kuo Hsiung̀

doi:10.1055/s-2005-873139

Cited by 30 publications

(26 citation statements)

References 12 publications

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“…In summary, our studies, in agreement with previous investigations on sesquiterpene lactones isolated from Asteraceae species [33,34], provide an in vitro scientific support for the use of several Asteraceae species for cancer-related diseases [35], and indicate that O. cynarocephalum may be considered a source of compounds for the prevention and treatment of neoplastic diseases, including melanoma.…”

Section: Resultssupporting

confidence: 90%

Phytochemical Profile and Apoptotic Activity of Onopordum cynarocephalum

et al. 2012

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A phytochemical investigation of acetone and chloroform extracts of the aerial parts of Onopordum cynarocephalum Boiss. et Blanche was carried out. It led to the isolation of two new sesquiterpenes, the elemane aldehyde (2) and the eudesmane (11), together with 15 known compounds: two lignans (1 and 15) and 13 sesquiterpenes (3-10, 12-14, 16, 17). The structures were elucidated by spectroscopic analyses, especially 1D and 2D NMR spectra. The anti-growth effect against three human melanoma cell lines, M14, A375, and A2058, of the different extracts and compounds of O. cynarocephalum was also investigated. Among them, the chloroform extract exhibited the strongest biological activity, while the most active compounds were the lignan arctigenin (1), and the sesquiterpenes, compounds 3, 5, and 6 belonging to the elemane type, and 7 belonging to the eudesmane type. Our data also demonstrate that acetone and chloroform extracts induce, in the A375 cell line, apoptotic cell death that could be related to an overall action of the compounds present, but in particular to the lignans arctigenin (1) and the sesquiterpenes compounds 3-8 and 16. In fact, these molecules were able to induce a high DNA fragmentation, correlated to a significant increase of the caspase-3 enzyme activity. Furthermore, apoptosis appears to be mediated, at least in part, via PTEN activity and the inhibition of Hsp70 expression.

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Section: Resultssupporting

confidence: 90%

Phytochemical Profile and Apoptotic Activity of Onopordum cynarocephalum

et al. 2012

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“…19 was active against 1A9, KB and KB-VIN. 83 showed good activity for all the lines except A549, and 66 and 70 were shown to be the best with IC 50 < 1 lM (Bruno et al, 2005b). Cnicin (19) showed inhibition of NF-jB and inhibition of iNOS activity with IC 50 values of 1.8 and 6.5 lM, respectively.…”

Section: Antitumor and Cytotoxicmentioning

confidence: 99%

Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C NMR spectral data and biological properties

et al. 2013

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“…Sesquiterpene lactones are one class of natural compounds that display cytotoxic activities and different components purified from various sources have been found to efficiently kill cancer cells [5][6][7][8][9][10][11][12][13]. Depending on the source of the isolated compounds and the tumor entities tested, the related mechanisms of sesquiterpene lactone-induced apoptosis are multifaceted, including inhibition of NF-κB, accumulation of reactive oxygen species (ROS), cell cycle arrest, induction of endoplasmic reticulum stress, and activation of caspase 8.…”

Section: Introductionmentioning

confidence: 99%

Antimyeloma activity of the sesquiterpene lactone cnicin: impact on Pim-2 kinase as a novel therapeutic target

et al. 2011

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Despite recent advances in therapy, multiple myeloma, the second most common hematologic tumor in the Western world, is still incurable. Identification of substances that display a wide range of tumor-killing activities and target cancer-specific pathways constitute a basis for the development of novel therapies. In this study, we investigate the cytotoxic effect of the natural substance cnicin in multiple myeloma. Cnicin treatment reveals potent antiproliferative effects and induces cell death in cell lines and primary myeloma cells even in the presence of survival cytokines and the tumor microenvironment. Other cell lines of hematopoietic origin also succumb to cell death whereas stromal cells and endothelial cells are unaffected. We show that activation of caspases, accumulation of reactive oxygen species and downregulation of nuclear factor kappa-light-chain-enhancer of activated B cell contribute to the cytotoxic effects of cnicin. Microarray analysis reveals downregulation of Pim-2, a serine/threonine kinase. We provide evidence that Pim-2 constitutes a new survival kinase for myeloma cells in vitro and is highly expressed in malignant but not in normal plasma cells in vivo. Combining cnicin with current standard or experimental therapeutics leads to enhanced cell death. Thus, our data indicate that cnicin induces myeloma cell death via several pathways and reveals Pim-2 as a novel target. These findings provide a rational for further evaluation of cnicin as a new anti-tumor drug and underline the potential of sesquiterpene lactones in tumor therapy.

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Cytotoxic Activity of Some Natural and Synthetic Sesquiterpene Lactones

Cited by 30 publications

References 12 publications

Phytochemical Profile and Apoptotic Activity of Onopordum cynarocephalum

Phytochemical Profile and Apoptotic Activity of Onopordum cynarocephalum

Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C NMR spectral data and biological properties

Antimyeloma activity of the sesquiterpene lactone cnicin: impact on Pim-2 kinase as a novel therapeutic target

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