Potential anticancer activity of young Carpinus betulus leaves
Cieckiewicz, Ewa ; Angenot, Luc ; et al
in Planta Medica (2012, August), 78(11), 1178Detailed reference viewed: 49 (11 ULg)
N-Aryl-N'-(chroman-4-yl)ureas and thioureas display in vitro anticancer activity and selectivity on apoptosis-resistant glioblastoma cells: screening, synthesis of simplified derivatives, and structure-activity relationship analysis.
Goffin, Eric ; ; et al
in European Journal of Medicinal Chemistry (2012), 54
A series of chroman derivatives previously reported as potassium channel openers, as well as some newly synthesized simplified structures, were examined for their in vitro effects on the growth of three ... [more ▼]
A series of chroman derivatives previously reported as potassium channel openers, as well as some newly synthesized simplified structures, were examined for their in vitro effects on the growth of three human high-grade glioma cell lines: U373, T98G, and Hs683. Significant in vitro growth inhibitory activity was observed with 2,2-dimethylchroman-type nitro-substituted phenylthioureas, such as compounds 4o and 4p. Interestingly, most tested phenylureas were found to be slightly less active, but more cell selective (normal versus tumor glial cells, such as 3d, 3e, and 3g), thus less toxic, than the corresponding phenylthioureas. No significant differences were observed in terms of chroman-derivative-induced growth inhibitory effects between glioma cells sensitive to pro-apoptotic stimuli (Hs683 glioma cells) and glioma cells associated with various levels of resistance to pro-apoptotic stimuli (U373 and T98G glioma cells), a feature that suggests non-apoptotic-mediated growth inhibition. Flow cytometry analyses confirmed the absence of pro-apoptotic effects for phenylthioureas and phenylureas when analyzed in U373 glioma cells and demonstrated U373 cell cycle arrest in the G0/G1 phase. Computer-assisted phase-contrast videomicroscopy revealed that 3d and 3g displayed cytostatic effects, while 3e displayed cytotoxic ones. As a result, this work identified phenylurea-type 2,2-dimethylchromans as a new class of antitumor agents to be further explored for an innovative therapeutic approach for high-grade glioma and/or for a possible new mechanism of action. [less ▲]Detailed reference viewed: 32 (3 ULg)
Sparc-like protein 1 is a new marker of human glioma progression.
Turtoi, Andrei ; ; et al
in Journal of Proteome Research (2012), 11(10), 5011-21
High-grade gliomas (glioblastomas) are the most common and deadly brain tumors in adults, currently with no satisfactory treatment available. Apart from de novo glioblastoma, it is currently accepted that ... [more ▼]
High-grade gliomas (glioblastomas) are the most common and deadly brain tumors in adults, currently with no satisfactory treatment available. Apart from de novo glioblastoma, it is currently accepted that these malignancies mainly progress from lower grade glial tumors. However, the molecular entities governing the progression of gliomas are poorly understood. Extracellular and membrane proteins are key biomolecules found at the cell-to-cell communication interface and hence are a promising proteome subpopulation that could help understand the development of glioma. Accordingly, the current study aims at identifying new protein markers of human glioma progression. For this purpose, we used glial tumors generated orthotopically with T98G and U373 human glioma cells in nude mice. This setup allowed also to discriminate the protein origin, namely, human (tumor) or mouse (host). Extracellular and membrane proteins were selectively purified using biotinylation followed by streptavidin affinity chromatography. Isolated proteins were digested and then identified and quantified employing 2D-nano-HPLC-MS/MS analysis. A total of 23 and 27 up-regulated extracellular and membrane proteins were identified in the T98G and U373 models, respectively. Approximately two-thirds of these were predominantly produced by the tumor, whereas the remaining proteins appeared to be mainly overexpressed by the host tissue. Following extensive validation, we have focused our attention on sparc-like protein 1. This protein was further investigated using immunohistochemistry in a large collection of human glioma samples of different grades. The results showed that sparc-like protein 1 expression correlates with glioma grade, suggesting the possible role for this protein in the progression of this malignancy. [less ▲]Detailed reference viewed: 31 (4 ULg)
Galectin-1 in Melanoma Biology and Related Neo-Angiogenesis Processes.
; ; et al
in Journal of Investigative Dermatology (2012)
Aggressiveness of advanced melanomas relates in part to their marked propensity to develop neoangiogenesis and metastases. Among its numerous pro-cancer roles, galectin (gal)-1 expressed and/or secreted ... [more ▼]
Aggressiveness of advanced melanomas relates in part to their marked propensity to develop neoangiogenesis and metastases. Among its numerous pro-cancer roles, galectin (gal)-1 expressed and/or secreted by both cancer and endothelial cells stimulates proliferation and angiogenesis. This study first shows that gal-1 is more highly expressed at both mRNA and protein levels than its congeners in melanomas and particularly in advanced lesions. The roles of gal-1 were further investigated in vivo in the highly proliferating and vascularized pseudometastatic B16F10 mouse melanoma model using stable knockdown B16F10 cells and wild-type versus gal-1 knockout mice, and then in vitro in B16F10 tumoral and lung microvascular cells. Gal-1 depletion in the B16F10 tumor cells but not in the tumor-bearing mice significantly increased melanoma-bearing mice survival. Tumor-derived gal-1 thus seems to have more critical roles than the host-derived one. In fact, gal-1 displays distinct effects on the H-Ras-dependent p53/p21 pathways: in primary lung microvessel endothelial cells, gal-1 seems to be involved in the maintenance of senescent status through the induction of both p53 and p21 while it stimulates B16F10 cancer cell proliferation through a p53/p21 decrease. Altogether, these data point to gal-1 as a potential target to combat melanomas.Journal of Investigative Dermatology advance online publication, 24 May 2012; doi:10.1038/jid.2012.142. [less ▲]Detailed reference viewed: 31 (6 ULg)
WATER SOLUBLE CURCUMIN COMPOSITIONS FOR USE IN ANTI-CANCER AND ANTI-INFLAMMATORY THERAPY
; Serteyn, Didier ; et al
The present invention relates to the medical field. In a first aspect the present invention relates to novel water soluble cyclodextrin-curcumin complexes having a pharmacological activity, in particular ... [more ▼]
The present invention relates to the medical field. In a first aspect the present invention relates to novel water soluble cyclodextrin-curcumin complexes having a pharmacological activity, in particular an anti-tumour and/or anti-inflammatory activity, and improved physico-chemical properties. In a second aspect, the present invention relates to a method for preparation of said water soluble curcumin derivatives. The invention further relates in a third aspect to a pharmaceutical composition comprising an effective amount of said water soluble curcumin derivatives. In a fourth aspect, the present invention concerns the use of said water soluble cucumin derivatives as a medicament and the use of said water soluble curcumin derivatives for the preparation of a medicament for the treatment of cancer and inflammatory diseases. In a fifth aspect, the present invention relates to the use of a pharmaceutical composition comprising said water soluble curcumin derivatives in the treatment of cancer and inflammatory diseases and to a new pharmaceutical composition comprising said water soluble curcumin derivatives. [less ▲]Detailed reference viewed: 157 (13 ULg)
Quercetin inhibits a large panel of kinases implicated in cancer cell biology.
; ; et al
in International Journal of Oncology (2011), 38
Flavonoids are polyphenolic secondary metabolites from plants that possess a common phenylbenzopyrone structure (C6-C3-C6). Depending upon variations in their heterocyclic C-ring, flavonoids are ... [more ▼]
Flavonoids are polyphenolic secondary metabolites from plants that possess a common phenylbenzopyrone structure (C6-C3-C6). Depending upon variations in their heterocyclic C-ring, flavonoids are categorised into one of the following groups: flavones, flavonols, flavanones, flavanols, anthocyanidins, isoflavones or chalcones. Flavonols include, among others, the molecules quercetin, myricetin and kaempferol. The anticancer activity of flavonols was first attributed to their electron-donating ability, which comes from the presence of phenolic hydroxyl groups. However, an emerging view is that flavonoids, including quercetin, may also exert modulatory actions in cells by acting through the protein kinase and lipid kinase signalling pathways. Data from the current study showed that 2 μM quercetin, a low concentration that represents less than 10% of its IC50 growth inhibitory concentration as calculated from the average of eight distinct cancer cell lines, decreased the activity of 16 kinases by more than 80%, including ABL1, Aurora-A, -B, -C, CLK1, FLT3, JAK3, MET, NEK4, NEK9, PAK3, PIM1, RET, FGF-R2, PDGF-R· and -Rß. Many of these kinases are involved in the control of mitotic processes. Quantitative video microscopy analyses revealed that quercetin displayed strong anti-mitotic activity, leading to cell death. In conclusion, quercetin partly exerts its anticancer activity through the inhibition of the activity of a large set of kinases. Quercetin could be an interesting chemical scaffold from which to generate novel derivatives possessing various types of antikinase activities. [less ▲]Detailed reference viewed: 38 (1 ULg)
Isostrychnopentamine, an Indolomonoterpenic Alkaloid from Strychnos usambarensis, with Potential Antitumor Activity against Apoptosis-Resistant Cancer Cells
; ; Angenot, Luc et al
in International Journal of Oncology (2010), 36Detailed reference viewed: 60 (19 ULg)
Simple di- and trivanillates exhibit cytostatic properties toward cancer cells resistant to pro-apoptotic stimuli.
; ; Kerff, Frédéric et al
in Bioorganic & Medicinal Chemistry (2010), 18(11), 3823-33
A series of 33 novel divanillates and trivanillates were synthesized and found to possess promising cytostatic rather than cytotoxic properties. Several compounds under study decreased by >50% the ... [more ▼]
A series of 33 novel divanillates and trivanillates were synthesized and found to possess promising cytostatic rather than cytotoxic properties. Several compounds under study decreased by >50% the activity of Aurora A, B, and C, and WEE1 kinase activity at concentrations <10% of their IC(50) growth inhibitory ones, accounting, at least partly, for their cytostatic effects in cancer cells and to a lesser extent in normal cells. Compounds 6b and 13c represent interesting starting points for the development of cytostatic agents to combat cancers, which are naturally resistant to pro-apoptotic stimuli, including metastatic malignancies. [less ▲]Detailed reference viewed: 90 (2 ULg)
In Vitro Anticancer Potential of Tree Extracts from the Walloon Region Forest.
Frederich, Michel ; ; Cieckiewicz, Ewa et al
in Planta Medica (2009), 75(15), 1634-1637
Forty-eight extracts from 16 common Belgian trees from the Walloon Region forest were evaluated for IN VITRO growth inhibitory activity against the human LoVo colon cancer, PC3 prostate cancer, and U373 ... [more ▼]
Forty-eight extracts from 16 common Belgian trees from the Walloon Region forest were evaluated for IN VITRO growth inhibitory activity against the human LoVo colon cancer, PC3 prostate cancer, and U373 glioblastoma cell lines. Our study was performed with the aim of selecting plant candidates in order to later isolate new anticancer compounds from an easily affordable tree material. Extracts from ALNUS GLUTINOSA (stem bark), CARPINUS BETULUS (leaves and stem bark), CASTANEA SATIVA (stem bark), FAGUS SYLVATICA (leaves), ILEX AQUIFOLIUM (leaves), LARIX DECIDUA (leaves), QUERCUS PETRAEA (stem bark), and QUERCUS ROBUR (leaves) showed for the first time potent IN VITRO growth inhibitory activity and could become easily affordable sources of potential new anticancer agents. Root extracts from ROBINIA PSEUDOACACIA, already known for containing cytotoxic lectins, also showed interesting activity. [less ▲]Detailed reference viewed: 83 (18 ULg)