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Showing papers on "Taspine published in 2011"


Journal ArticleDOI
TL;DR: The results suggest that EGFR activated by EGF and its downstream signaling pathways proteins could be downregulated by taspine in a dose-dependent manner.
Abstract: EGFR, as a critical signaling pathway in many human tumors, has become an important target of cancer drug design. Taspine has shown meaningful angiogenesis activity in previous studies. This paper is to investigate the antitumor action of taspine by modulating the EGFR signaling pathway. The study determined the expression of key signaling molecules of EGFR (EGFR, Akt, p-Akt, Erk, and p-Erk) by Western blot and real-time PCR and analyzed their correlations with subsequent reactions. In addition, the cell proliferation, migration, and EGF production were examined by MTT, transwell system, and ELISA. The antitumor activity in vivo was carried out by xenograft in athymic mice. The results showed that taspine could inhibit A431 and Hek293/EGFR cell proliferation and A431 cell migration as well as EGF production. Compared to the negative control, EGFR, Akt, and phosphorylation of Akt were significantly inhibited by taspine treatment in A431 and HEK293/EGFR cells. Consistent with the inhibition of Akt activity, Erk1/2 and its phosphorylation were reduced. Moreover, taspine inhibited A431 xenograft tumor growth. These results suggest that EGFR activated by EGF and its downstream signaling pathways proteins could be downregulated by taspine in a dose-dependent manner. The antitumor mechanism of taspine through the EGFR pathway lies in the ability to inhibit A431 cell proliferation and migration by reducing EGF secretion. This occurs through the repression of EGFR which mediates not only MAPK (Erk1/2) but also Akt signals.

25 citations


Journal ArticleDOI
TL;DR: The results indicated that the majority of the compounds exhibited anticancer activity equivalent to or greater than the positive control, and provided a good starting point for further development of symmetrical biphenyl derivatives as potential novel anticancer agents.
Abstract: It has been demonstrated that taspine derivatives act as anticancer agents, thus we designed and synthesized a novel class of symmetrical biphenyl derivatives. We evaluated the cytotoxicity and antitumor activity of biphenyls against five human tumor and normal cell lines. The results indicated that the majority of the compounds exhibited anticancer activity equivalent to or greater than the positive control. Compounds (11) and (12) demonstrated the most potent cytotoxic activity with IC50 values between 19.41 μM and 29.27 μM. The potent antiproliferative capabilities of these compounds against ECV304 human transformed endothelial cells indicated that these biphenyls could potentially serve as antiangiogenic agents. We also reviewed the relationship between structure and activity based on the experimental results. Our findings provide a good starting point for further development of symmetrical biphenyl derivatives as potential novel anticancer agents.

20 citations


Journal ArticleDOI
Yanmin Zhang1, Jie Zhang1, Bingling Dai1, Nan Wang1, Langchong He1 
TL;DR: It is demonstrated that tas41 can inhibit the proliferation of, and induce apoptosis in, Caco-2 cells by activating caspase-3, caspases-8 and caspasing-9, downregulating the expressions of VEGF, upregulate the ratio of bax/bcl-2 and RT-PCR.

15 citations


Journal ArticleDOI
TL;DR: It is demonstrated that taspine can inhibit the proliferation of, and induce apoptosis in, A431 cells by activating caspase‐3 expression and up‐regulating the ratio of Bax/Bcl‐2 in A431 Cells.
Abstract: Taspine is an active component isolated from Radix et Rhizoma Leonticis. It has been shown that taspine can inhibit tumour angiogenesis. However, how it inhibits the proliferation of, and induces apoptosis in, A431 cells is unknown. The study investigated the effects of taspine on the proliferation and apoptosis in the A431 cell line using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, transmission electron microscopy (TEM), western blotting (WB) and real-time reverse transcription-polymerase chain reaction (PCR). Changes in microstructure, cell cycle and protein expressions of caspase-3, cleaved caspase-3, cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), Bcl-2 and Bax were observed after treatment of A431 cells with taspine. Taspine could inhibit the growth of, and induce apoptosis in, A431 cells in a dose-dependent manner. The cell cycle was significantly stopped at S phase. Nuclear karyopyknosis, chromatin agglutination and typical apoptotic bodies were found in A431 cells. There was a decrease in the expression of Bcl-2, whereas the expression of caspase-3, cleaved caspase-3, CDK2, CDK4 and Bax increased. These data demonstrated that taspine can inhibit the proliferation of, and induce apoptosis in, A431 cells by activating caspase-3 expression and up-regulating the ratio of Bax/Bcl-2 in A431 cells. Copyright © 2010 John Wiley & Sons, Ltd.

13 citations


Journal ArticleDOI
TL;DR: Results suggested that taspine might serve as a promising candidate of ER antagonist in the treatment of oestrogen-independent breast cancer.

12 citations


Journal ArticleDOI
TL;DR: Results indicated that taspine, with antitumor activity, could interact with the cell, act on EGFR at the cell membrane, and inhibit cell proliferation by down-regulating EGFR protein and mRNA expression.
Abstract: Taspine was isolated for the first time from Radix et Rhizoma Leonticis. Epidermal growth factor receptor (EGFR) is important in cell growth and differentiation and has become an important target in anti-cancer drug design. In this study, we found taspine could inhibit proliferation of A431 and HEK293/EGFR cells. To investigate whether it could enter the cell or acted on the cell membrane receptor, a cell-based assay was established to determine the concentration of taspine in A431 and HEK293/EGFR cells using high-performance liquid chromatography–mass spectrometry (HPLC–MS). The inhibitory effects of taspine on EGFR expression and mRNA expression were also investigated. The HPLC–MS results showed that taspine decreased in the supernatant liquid, and increased in the cell lysate, which indicated that taspine could enter the cell or act on the cell membrane receptor. Subsequent analysis using a cell-membrane chromatography (CMC) assay showed that taspine could act on EGFR at the cell membrane. In addition, ELISA and reverse transcriptase polymerase chain reaction (RT-PCR) assays showed that taspine inhibited proliferation, EGFR protein, and EGFR mRNA expression in A431 and HEK293/EGFR cells. These results indicated that taspine, with antitumor activity, could interact with the cell, act on EGFR at the cell membrane, and inhibit cell proliferation by down-regulating EGFR protein and mRNA expression.

6 citations


Journal Article
TL;DR: The taspine derivative Tas-D1 can inhibit the growth of human Liver cancer SMMC7721 cell and change cell cycle, which may be related to the inhibition of EGF and VEGF expression.
Abstract: OBJECTIVE To analyse the inhibition effect of taspine derivatives on human Liver cancer SMMC7721 cell and its mechanism. METHODS The effects of five taspine derivatives on SMMC7721 cell growth were determined by MTT. The flow cytometry was used to determine the cell cycle. The effects of Tas-D1 on the EGF and VEGF in SMMC7721 cell were determined by ELISA. The mRNA level of EGF and VEGF in SMMC7721 cell was determined by RT-PCR. RESULTS The MTT assay demonstrated that the taspine derivative Tas-D1 significantly inhibited the growth of SMMC7721 cell in a dose-dependent manner. Cell was stopped at S phase by Tas-D1. Tas-D1 inhibited the expression of EGF and VEGF and their mRNA in a dose-dependent manner (P<0.05). CONCLUSIONS The taspine derivative Tas-D1 can inhibit the growth of human Liver cancer SMMC7721 cell and change cell cycle, which may be related to the inhibition of EGF and VEGF expression.

2 citations