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Strong Cytotoxic Activity (strong + cytotoxic_activity)

Distribution by Scientific Domains
Medical Sciences40%
Life Sciences40%

Selected Abstracts

Two New Pregnanone Derivatives with Strong Cytotoxic Activity from Pachysandra axillaris

CHEMISTRY & BIODIVERSITY, Issue 7 2005
Ming-Hua Qiu
Two new, bioactive, pregnane-based natural products, pachysanonin (=3,,11,,12,)-12-acetoxy-3-(dimethylamino)-11-[(3,4-dimethylpent-3-enoyl)oxy]pregnan-20-one; 1) and pachysanone (=(11,,12,)-12-acetoxy-11-[(3,4-dimethylpent-3-enoyl)oxy]pregnan-3,20-dion; 2) have been isolated from Pachysandra axillaris. Their structures were determined by spectroscopic methods, and, in the case of 2, by single-crystal X-ray crystallography (Figure). Compound 2 showed significant antitumor activity against Lewis lung carcinoma (LCC) tumor cells, with an IC50 value of 0.020±0.006,,g/ml, which is equal or even lower than those of the well-known natural antitumor agents harringtonine (0.02), homoharringtonine (0.15), and adriamycin (0.06,,g/ml; positive control). [source]

Production of Taxol fromPhyllosticta spinarum, an endophytic fungus ofCupressus sp.

ENGINEERING IN LIFE SCIENCES (ELECTRONIC), Issue 4 2008
R. Senthil Kumaran
Abstract Taxol production during the cultivation on a modified liquid and potato dextrose broth medium was indicated for the first time to occur in Phyllosticta spinarum, an endophytic fungus isolated from the needles of Cupressus sp. The presence of taxol in the fungal culture filtrate was confirmed by chromatographic and spectroscopic methods of analysis. The amount of taxol produced by this fungus was quantified by high performance liquid chromatography. The maximum amount of taxol production was obtained in this fungus when grown on M1D medium (235,,g/L) followed by PDB medium (125,,g/L). The results indicate that P.,spinarum is an excellent candidate for taxol production. The production rate was 4.7,×,103 -fold higher than that found in the culture broth of an earlier reported fungus, Taxomyces andreanae. The fungal taxol extracted also showed a strong cytotoxic activity in the in vitro culture of human cancer cells tested in an apoptotic assay. [source]

DNAX accessory molecule-1 (CD226) promotes human hepatocellular carcinoma cell lysis by V,9V,2 T cells

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2009
Olivier Toutirais
Abstract Human V,9V,2 T lymphocytes can be activated by nonpeptidic antigens such as the mevalonate pathway-derived isopentenyl pyrophosphate or synthetic phosphoantigen such as bromohydrin pyrophosphate. They display a strong cytotoxic activity against several tumor types, including hepatocellular carcinoma (HCC). Little is known about the mechanisms underlying V,9V,2 T-cell recognition of tumor cells, but there is strong evidence that activating NK receptors play a role in ,, T-cell cytotoxicity. In this study, we showed that the two NK receptors DNAX accessory molecule-1 (DNAM-1) and CD96 were expressed by V,9V,2 T cells. The ligands Nectin-like-5 specific of both DNAM-1 and CD96, and also Nectin-2, an additional ligand of DNAM-1, were present on all HCC cell lines analyzed. Furthermore, we demonstrated by mAb-mediated masking experiments that cytotoxicity against HCC cells as well as IFN-, production in ,, T cells were dependent on DNAM-1. Our experiments indicated that Nectin-like-5 but not Nectin-2 was involved in DNAM-1-dependent ,, T-cell functions. We did not reveal a role for CD96 in the killing of HCC cells. Finally, we showed by combined mAb-mediated blockade that DNAM-1 and NKG2D could cooperate in the cell lysis of HCC. [source]

Effects of climacostol on normal and tumoral mammalian cell lines

THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 2 2005
FEDERICO BUONANNO
Climacostol, 1,3-dihydroxy-5-[(Z)-2,-nonenyl]benzene, is a natural toxin contained in the extrusomal cortical granules of the heterotrich ciliate Climacostomum virens. It is used for chemical defence against predators such as the raptorial ciliate Dileptus margaritifer and its cytotoxic activity has been assessed on several species of ciliates such as Didinium nasutum, Paramecium caudatum, and Blepharisma japonicum (Miyake et al. 2003, Europ. J. Protistol., 39:25,36). On the basis of its chemical structure, climacostol may be classified into the large group of natural compounds known as resorcinolic lipids, that show antimicrobial, antiparasitic, and antitumoral activities (Kozubek et al. 2003, Cell Moll. Biol. Lett., 6:351,355). To explore the possibility to use climacostol in medical applications, we examined the effects of chemically synthesized climacostol (Masaki et al. 2004, Tetrahedron, 60:7041,7048) on the growth and proliferation of tumoral and normal mammalian cell lines: (1) human promyelocytic leukaemia cells, HL60; (2) human squamous carcinoma cells, A431; and (3) non-tumoral cells derived from mice Leydig cells, TM3. It was observed that (1) a concentration of 10 ,g/ml of climacostol exerts a strong cytotoxic activity on all cell lines used; (2) at lower concentrations of 10 ng/ml and 1 ng/ml, the effect of climacostol is limited to the inhibition of the cell growth; and (3) the normal TM3 cells are more resistant to climacostol than the two tumoral HL60 and A431cell lines. The dose-dependent cytotoxic effects of climacostol encourage further investigation on the potential use of this ciliate toxin as an anti-cancer chemical. [source]

Successful In Vitro Priming of EBV-Specific CD8+ T Cells Endowed with Strong Cytotoxic Function from T Cells of EBV-Seronegative Children

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2006
P. Comoli
Epstein-Barr virus (EBV)-seronegative transplant recipients are at high risk of developing EBV-associated post-transplant lymphoproliferative disorder (PTLD), and would maximally benefit from an EBV-directed T-cell therapy for prevention or treatment of PTLD. So far, efforts to activate CD8+ EBV-specific cytotoxic T lymphocytes (CTL) endowed with high specific cytotoxicity from EBV-seronegative children have failed. We compared the CD8+ CTL priming efficiency of three different modified activation protocols, based on lymphoblastoid cell lines (LCL) stimulation potentially enhanced by either LCL presentation through dendritic cells, or selection of IFN-,+ cultured cells, or culture in the presence of rhIL-12 and rhIL-7, according to the standard protocol for reactivation of EBV-specific CTL. We found that only specific LCL stimulation in the presence of rhIL-12 and rhIL-7 was able to reproducibly expand EBV-specific CD8+ CTL endowed with strong cytotoxic activity from truly EBV-seronegative children. The lines thus activated, which included specificities toward EBV latent and lytic proteins, showed high percentage CD8+ T cells, with <10% naïve CD8+/CCR7+/CD45RA+ cells. Overall, the total number of CD8+ central memory cells, and of CCR7 T-cell effectors was comparable to that observed in healthy EBV-seropositive controls. In conclusion, it is feasible to activate EBV-specific CD8+ CTL with suitable characteristics for in vivo employment from EBV-seronegative children. [source]