Article

Mitochondria-dependent apoptosis of activated T lymphocytes induced by astin C, a plant cyclopeptide, for preventing murine experimental colitis.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing 210093, China.
Biochemical pharmacology (Impact Factor: 4.25). 05/2011; 82(3):260-8. DOI: 10.1016/j.bcp.2011.04.013
Source: PubMed

ABSTRACT Facilitating T-cell apoptosis is implicated as an effective therapeutic strategy for treatment of T cell-mediated disease, including inflammatory bowel disease. Here, we report that astin C, a plant cyclopeptide isolated from the roots of Aster tataricus (Compositae), induced apoptosis of activated T cells in a mitochondria-dependent but Fas-independent manner in that such activity was still observed in T cells from Fas-mutated MRLlpr/lpr mice. Although caspase 8 was not activated, astin C treatment led to the cleavage of caspase 9 and caspase 3, the upregulation of Bad protein expression as well as release of cytochrome c in activated T cells. Astin C did not induce the expression of GRP78 and GADD153, excluding involvement of endoplasmic reticulum stress-mediated pathway. Moreover, oral administration of astin C protected mice against TNBS-induced colonic inflammation, as assessed by a reduced colonic weight/length ratio and histological scoring. Administering astin C significantly decreased serum levels of TNF-α, IL-4 and IL-17, accompanied with the induction of apoptosis in activated T cells in vivo. The results demonstrate, for the first time, the ability of astin C to induce apoptosis in activated T cells and its potential use in the treatment of colonic inflammation.

0 Bookmarks
 · 
69 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To determine whether microwave (MW) radiation induces neural cell apoptosis, differentiated PC12 cells and Wistar rats were exposed to 2.856GHz for 5min and 15min, respectively, at an average power density of 30 mW/cm(2). JC-1 and TUNEL staining detected significant apoptotic events, such as the loss of mitochondria membrane potential and DNA fragmentation, respectively. Transmission electron microscopy and Hoechst staining were used to observe chromatin ultrastructure and apoptotic body formation. Annexin V-FITC/PI double staining was used to quantify the level of apoptosis. The expressions of Bax, Bcl-2, cytochrome c, cleaved caspase-3 and PARP were examined by immunoblotting or immunocytochemistry. Caspase-3 activity was measured using an enzyme-linked immunosorbent assay. The results showed chromatin condensation and apoptotic body formation in neural cells 6h after microwave exposure. Moreover, the mitochondria membrane potential decreased, DNA fragmentation increased, leading to an increase in the apoptotic cell percentage. Furthermore, the ratio of Bax/Bcl-2, expression of cytochrome c, cleaved caspase-3 and PARP all increased. In conclusion, microwave radiation induced neural cell apoptosis via the classical mitochondria-dependent caspase-3 pathway. This study may provide the experimental basis for further investigation of the mechanism of the neurological effects induced by microwave radiation.
    International journal of medical sciences 01/2014; 11(5):426-35. · 2.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Six new shionane-type triterpenes, astershionones A-F (1-6), were obtained from the roots and rhizomes of Aster tataricus. Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS data. The absolute configuration of 1 was determined by single crystal X-ray diffraction analysis and CD analysis. 3 showed inhibitory activity against HBsAg and HBeAg secretion with IC50 values of 23.0 and 23.1μM, and cytotoxicity against HepG 2.2.15 cells with CC50 value of 170.5μM. 3 also exhibited inhibitory activity against HBV DNA replication with IC50 value of 22.4μM.
    Fitoterapia 01/2014; · 2.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this Letter, the anticancer activity of novel rosin-derivatives introducing indicated side chains at position C18 of dehydroabietic acid (DHAA) was reported. Gratifyingly, all of these derivatives showed significantly cytotoxicity toward diverse human carcinoma cell lines. We found the compound 4 could induce cell membrane damage at high concentration as well as cell apoptosis at low concentration. However, compound 5, attachment of quinidine to dehydroabietic acid via thiourea bond, only induced apoptotic cell death. In addition, all these active compounds induced apoptosis mainly through mitochondrial-dependent pathway. Interestingly, compound 5 exhibited the highest anticancer activity and little toxicity to normal cells compared with the other derivatives. Therefore, 5 merits further investigation as a potential agent for future anticancer treatment.
    Bioorganic & medicinal chemistry letters 05/2013; · 2.65 Impact Factor

Full-text (2 Sources)

View
0 Downloads
Available from
Jul 1, 2014