Activity of novel plant extracts against medullary thyroid carcinoma cells. (1/9)

BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare calcitonin-producing tumor, derived from the parafollicular C-cells of the thyroid. MTC is known to be relatively insensitive to conventional chemotherapy. MATERIALS AND METHODS: Eight cell lines were established from MTCs; each showed an up-regulation of Bcl-2. We investigated ten agents from plants of the genera Stemona (Stemonaceae), Aglaia (Meliaceae) and Artemisia (Asteraceae) for their effects on proliferation and apoptotic rates. Extracts have been used in traditional Chinese medicine; however, no experience on their effects on medullary thyroid carcinomas has been reported so far. Growth kinetics and viability were examined using the Casy-1-Cell Counter & Analyzer and the WST-1-based cytotoxicity assay. Apoptosis was studied by DAPI staining, by measurement of caspase-3 activity and Bcl-2 expression. RESULTS: A strong antiproliferative effect was recognized in each Aglaia species and with Artesunate, whereas an enhancement of apoptosis was provoked particularly by Stemona tuberosa Lour. CONCLUSION: The activity of the novel plant extracts possiby offers a new approach towards successful chemotherapy of the so far chemo-resistant medullary thyroid carcinoma.  (+info)

Rocaglamide derivatives are immunosuppressive phytochemicals that target NF-AT activity in T cells. (2/9)

Aglaia (family Meliaceae) plants are used in traditional medicine (e.g., in Vietnam) for the treatment of inflammatory skin diseases and allergic inflammatory disorders such as asthma. Inflammatory diseases arise from inappropriate activation of the immune system, leading to abnormal expression of genes encoding inflammatory cytokines and tissue-destructive enzymes. The active compounds isolated from these plants are derivatives of rocaglamide. In this study we show that rocaglamides are potent immunosuppressive phytochemicals that suppress IFN-gamma, TNF-alpha, IL-2, and IL-4 production in peripheral blood T cells at nanomolar concentrations. We demonstrate that rocaglamides inhibit cytokine gene expression at the transcriptional level. At the doses that inhibit cytokine production, they selectively block NF-AT activity without impairing NF-kappaB and AP-1. We also show that inhibition of NF-AT activation by rocaglamide is mediated by strong activation of JNK and p38 kinases. Our study suggests that rocaglamide derivatives may serve as a new source of NF-AT-specific inhibitors for the treatment of certain inflammatory diseases.  (+info)

Rocaglaol induces apoptosis and cell cycle arrest in LNCaP cells. (3/9)

Rocaglaol is a cytotoxic cyclopenta[b]benzofuran isolated from the bark of Aglaia crassinervia. It exhibited in vitro cytotoxic activity against Lu1, LNCaP and MCF-7 cells with ED50 values of 13.8, 23.0 and 9.2 nM, respectively. DAPI staining indicated that LNCaP cells treated with rocaglaol underwent apoptosis. In order to determine whether rocaglaol-induced apoptosis is mediated by the mitochondrial pathway, apoptosis-related mitochondrial-associated proteins were studied. Rocaglaol treatment induced Bax expression through 12 to 72 h of exposure, while Bcl-xl expression was slightly decreased through 48 h, and decreased more significantly by 72 h. Cleaved caspase-9 expression was detected at 72 h, and cleaved caspase-7 was increased through 48 to 72 h. Consequently, the large fragment (89 kDa) of PARP resulting from caspase cleavage was detected at 12, 24 and 48 h, and especially at 72 h. Cleaved PARP expression was also detected at 72 h. Since rocaglaol caused dose-dependent G2/M phase arrest of LNCaP cells as indicated by flow cytometric analysis, the protein levels of cell cycle-related genes were measured. Rocaglaol treatment (230 nM) did not change cyclin B after 24- to 60-h treatment. The expression of cdc2 was not changed and phospho-cdc2 (Tyr 15) increased after 36-, 48- and 60-h treatment. In addition, protein phosphatase Cdc25C, which functions as a mitotic activator by dephosphorylation of Cdc2, decreased in a time-dependent manner after rocaglaol treatment. Taken together, these results suggest that rocaglaol is a potent anticancer drug that induces apoptosis of LNCaP cells through the mitochondrial pathway and its G2/M-phase cell cycle arrest is associated with the down-regulation of Cdc25C and the dephosphorylation of Cdc2.  (+info)

Ponapensin, a cyclopenta[bc]benzopyran with potent NF-kappaB inhibitory activity from Aglaia ponapensis. (4/9)

Two new compounds, a cyclopenta[bc]benzopyran, ponapensin (1), and an aglaialactone, 5,6-desmethylenedioxy-5-methoxy-aglalactone (2), together with nine known compounds were isolated from the CHCl(3) soluble extract of the leaves and twigs of Aglaia ponapensis. Their structures were established by spectroscopic data interpretation. Ponapensin (1) exhibited significant NF-kappaB inhibitory activity in an Elisa assay, and was found to be more potent than the positive control rocaglamide. All of the compounds isolated were also tested in a panel of human cancer cell lines, with the known sterol E-volkendousin (3) and methyl rocaglate (aglafoline) found to be the only active substances.  (+info)

Silvestrol, a potential anticancer rocaglate derivative from Aglaia foveolata, induces apoptosis in LNCaP cells through the mitochondrial/apoptosome pathway without activation of executioner caspase-3 or -7. (5/9)

The novel cyclopenta[b]benzofuran, silvestrol, isolated from the fruits and twigs of Aglaia foveolata, has been found to exhibit very potent in vitro cytotoxic activity against several human cancer cell lines. Furthermore, it was active in the in vivo P388 murine leukemia model. In this study, the mechanism of cytotoxicity mediated by silvestrol in the LNCaP (hormone-dependent human prostate cancer) cell line was investigated. Silvestrol induced an apoptotic response, disrupted the mitochondrial trans-membrane potential and caused cytochrome c release into the cytoplasm. Immunoblot analysis indicated that, at the protein level, silvestrol produced an increase of Bcl-xl phosphorylation with a concomitant increase of bak. Furthermore, caspase-2, -9 and -10 appeared to be involved in silvestrol-mediated apoptosis. In contrast, the involvement of caspase-3 and -7 was not detected, either by immunoblot or caspase-3/-7-like activity analysis, indicating that these pathways do not play a crucial role in silvestrol-induced apoptosis. To investigate the relative contribution of the caspases, inhibition of apoptosis with four different cell-permeable inhibitors was studied (Boc-D-Fmk, Z-VDVAD-FMK Z-LEHD-FMK and Z-AEVD-FMK). Only the general caspase inhibitor, Boc-D-Fmk, completely inhibited the formation of apoptotic bodies. In contrast, caspase-2 and caspase-9 selective inhibitors induced about a 40% reduced apoptotic response, whereas the caspase-10 selective inhibitor caused about a 60% reduction in apoptosis compared to silvestrol only treated cells. Taken together, the studies described herein demonstrate the involvement of the apoptosome/mitochondrial pathway and suggest the possibility that silvestrol may also trigger the extrinsic pathway of programmed cell death signaling in tumor cells.  (+info)

Isolation and characterization of minor analogues of silvestrol and other constituents from a large-scale re-collection of Aglaia foveolata. (6/9)

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An evaluation of the RNase H inhibitory effects of Vietnamese medicinal plant extracts and natural compounds. (7/9)

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The natural anticancer compounds rocaglamides inhibit the Raf-MEK-ERK pathway by targeting prohibitin 1 and 2. (8/9)

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