Antineoplastic cyclic astin analogues kill tumour cells via caspase-mediated induction of apoptosis.
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Astins, a family of cyclopentapeptides, isolated from the roots of a medicinal plant Aster tataricus (Compositae), show antitumour activity. Their chemical structures consist of a 16-membered ring system containing a unique beta,gamma-dichlorinated proline [Pro(Cl2)], other non-coded amino acid residues, and a cis conformation in one of the peptide bonds. The beta,gamma-dichlorinated proline residue is considered to play an important role in their antineoplastic activities in vitro on nasopharynx carcinoma (KB) cells and in vivo on sarcoma 180 ascites and P388 lymphocytic leukaemia in mice. The acyclic astins without Pro(Cl2) do not show antitumour activity against S-180 ascites in vivo, suggesting that the cyclic nature of astins plays an important role in their antitumour activities. We synthesized new astin-related cyclopeptides differing from the natural product for the presence of some non-proteinogenic amino acid residues: Aib, Abu, -S(beta3)-hPhe and a peptide bond surrogate (-SO2-NH-) and we tested for their antitumour effect. We observed cytotoxic effects of the newly synthesized cyclic astins, but not with the acyclic analogue astins. We also observed that the cyclic astin induced apoptosis in a human papillary thyroid carcinoma cell line (NPA cell line) and that apoptotis was associated with activation of caspases. The caspase family inhibitor, Z-Val-Asp-(OMe)-FMK, protected NPA cells from cyclic analogue astin-induced apoptosis. To determine which caspase was specifically activated, we assayed caspase activity in astin-treated cells in the presence of specific caspase and 8, 9 or 3 inhibitors, i.e. Z-IETD-FMK, Z-LEHD-FMK Z-DEVD-FMK, which inhibit caspases 8, 9 and 3, respectively. The data presented here show selective antineoplastic properties of the newly synthesized cyclic astins, and suggest, for the first time, a mechanism for their antineoplastic action through the activation of apoptotic pathway. (+info)
Distribution and ecology of cytotypes of the Aster amellus aggregates in the Czech Republic.
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BACKGROUND AND AIMS: Polyploidy is viewed as an important mechanism of sympatric speciation, but only a few studies have documented patterns of distribution and ecology of different cytotypes in their contact zone. Aster amellus agg. (Asteraceae) is one of the species with documented multiple ploidy levels. The aim of this study was to determine spatial distribution and ecology of two cytotypes, diploid (2n = 18) and hexaploid (2n = 54), of Aster amellus agg. at their contact zone in the Czech Republic. METHODS: Root-tip squashes and flow cytometry were used to determine the ploidy of 2175 individuals from 87 populations. To test whether some differences in ecology between the two ploidy levels exist, in each locality releves were recorded and abiotic conditions of the sites were studied by estimating potential direct solar radiation, Ellenberg indicator values and above-ground biomass. KEY RESULTS: Together with diploid and hexaploids, minorite cytotypes (triploid, pentaploid and nonaploid) were found. No significant ecological differences between diploid and hexaploid cytotypes were found. In spite of this, no population consisting of both of the two basic cytotypes was found. CONCLUSIONS: The results of this study show that the contact zone of diploid and hexaploid cytotypes in the Czech Republic is much more diffuse than indicated in previous records. Although populations of both cytotypes occur in close proximity (the closest populations of different cytotypes were 500 m apart), each individual population consists of only one basic ploidy level. This was unexpected since there are no clear differences in abiotic conditions between populations. Taken together with the absence of an intermediate tetraploid cytotype and with reference to published world distributional patterns of different ploidy levels, this suggests a secondary contact zone. Detailed genetic study is, however, necessary to confirm this. (+info)
Comparison of the antiinflammatory activities of three medicinal plants known as "meiduoluomi" in Tibetan folk medicine.
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Erigeron breviscapus (Vant.) Hand-mazz (EB), Erigeron multiradiatus (Lindl.) Benth (EM), and Aster brachytrichus Franch (AB), confused under the vernacular name "meiduoluomi" by native people and traditional healers, have been used for the treatment of meningitis, polyneuritis, hepatitis, adenolymphitis, and enteronitis in traditional Tibetan medicine. In this study, the antiinflammatory activity of methanol extracts of all three plants was investigated in the xylene-induced ear edema model, carrageenan-induced paw edema model, and cotton pellet-induced granuloma model. It was found that the methanolic extracts of both EB and EM had strong inhibitory effects on the acute phase of inflammation in carrageenan-induced paw edema in rats. On the other hand, the methanolic extract of EM showed stronger effects than those of EB in xylene-induced ear edema. In the chronic test, the methanolic extracts of EB and EM resulted in a significant reduction in granuloma weight in rats. In addition, myeloperoxidase (MPO) activity was strongly reduced in the EB-treated and EM-treated groups, which indicated that EB and EM can inhibit certain inflammatory modulator factors that cause neutrophil aggregation in inflamed tissue, e.g., nuclear factor-kappaB. However, the methanolic extracts of AB had no antiinflammatory effects in the tested models and MPO assay. The similar effects of EM and EB in tested models provided some scientific basis for the traditional usage of meiduoluomi in inflammatory disease. However, the results also suggest that further study is needed to investigate the antiinflammatory profile of AB and provide a scientific basis for the use of AB in inflammatory diseases. (+info)
Elevated atmospheric CO2 concentration ameliorates effects of NaCl salinity on photosynthesis and leaf structure of Aster tripolium L.
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