Tangutorine induces p21 expression and abnormal mitosis in human colon cancer HT-29 cells

Liu, B.P.L.; Chong, Edith Y.Y.; Cheung, Fanny M.; Duan, Jin‐Ao; Che, Chun‐Tao; Liu, W.K.

doi:10.1016/j.bcp.2005.04.024

Cited by 38 publications

(28 citation statements)

References 43 publications

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“…Because of p53 mutation on HT29 cells, upregulation of p21 after TXL treatment was independent of the status of its upstream cyclin kinase inhibitor p53. 23,32,33 Mostly, p53 influences the effectiveness of anticancer chemotherapy, which has played an important role in drug resistance that leads to low efficacy. 34,35 Therefore, seeking the p53-independent anticancer agent will be crucial.…”

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confidence: 99%

Regulation of p21, MMP-1, and MDR-1 Expression in Human Colon Carcinoma HT29 Cells by Tian Xian Liquid, a Chinese Medicinal Formula, In Vitro and In Vivo

et al. 2010

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Ethnopharmacological relevance. Tian-Xian liquid (TXL), a commercially available Chinese medicine decoction, has been used as an anticancer dietary agent for more than 10 years without reported side effects. Aim of the study. The safety and quality consistency of TXL and its mechanisms of action on antiproliferation, antimetastasis, and reversion of multidrug resistance (MDR) regimens were explored. Materials and methods. In this study, an atomic absorption spectrophotometer and reversed phase high performance liquid chromatography with photodiode array detection (HPLC-DAD) were used to evaluate the main toxic elements and the quality consistency among different batches of TXL extracts, respectively. HT29 human colon cancer cell line and tumor-bearing nude mice were used. TXL was provided by China-Japan Feida Union Company Limited. The effect of TXL on in vitro proliferation of HT29 human colon cancer cell line was examined. The percentages of treated cells distributed in different phases of the cell cycles were analyzed by flow cytometry. Antiproliferative effect after treatment with TXL was assessed by determination of the protein levels of p21, cyclinD1, PCNA, and cdk-2, which are the key regulators for cell cycle progression. Meanwhile, the protein levels of MMP-1 and MDR-1 (multidrug resistance protein-1) were also determined to assess the effect of TXL on antimetastasis and reversion of MDR regimen, respectively. Results. The contents of main toxic elements were lower in TXL extract compared with the standard set by the Department of Health of the Government of Hong Kong Special Administrative Region (SAR). Our HPLC results showed that the relative standard deviations of the amount of the 5 standards were less than 5% in different batches of TXL. Immunoblotting analysis revealed a dramatic induction of cyclin kinase inhibitor p21 as well as an inhibition of cyclinD1, PCNA, and cdk-2 in the TXL-treated in vitro models, thereby, impeding cell progression from G1/S phase. Results obtained from the in vivo study also demonstrated that TXL upregulated the protein level of p21 and downregulated the protein levels of MMP-1 and MDR-1. Conclusions. Results obtained from the present investigation not only demonstrate the safety and quality of TXL extract but also demonstrate that TXL possesses antiproliferative and antimetastatic activities and brings about reversion of MDR on HT29 cell and on xenografted tissue in tumor-implanted nude mice.

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confidence: 99%

Regulation of p21, MMP-1, and MDR-1 Expression in Human Colon Carcinoma HT29 Cells by Tian Xian Liquid, a Chinese Medicinal Formula, In Vitro and In Vivo

et al. 2010

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“…When cdc25C, which is a protein tyrosine phosphatase, dephosphorylates cdc2/p34, the Cdc2/Cyclin B1 complexes are formed, thereby allowing progression to mitosis (Gautier et al, 1991;Taylor and Stark, 2001). Results from numerous studies have shown that many chemotherapeutic agents induce G2/M-phase cell cycle arrest, aberrant mitosis and cell death in tumor cells (Liu et al, 2005;Chen et al, 2006;Jeong et al, 2003). In the present study, it was found that WEGS mediated HCT116 cell arrest at the G2/M phase, which led to the down-regulation of cyclinB1, Cdc2 and cdc25c.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies suggest that regulatory factors, such as extracellular signal-regulated kinases (ERKs), cell-cycle regulators, and the tumor suppressor gene p53, play a role in the progression of colon cancer Igney and Krammer, 2002;Sebolt-Leopold et al, 1999). Therefore, current colon cancer research is focused on the identifi cation of novel anticancer compounds that regulate cell proliferation, cell cycle progression and apoptosis (Liu et al, 2005). A recent study evaluated the effi cacy of naturally occurring chemopreventive compounds isolated from medicinal plants, which have few side effects, during different stages of CRC (Lu et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Gleditsia sinensis thorn extract inhibits human colon cancer cells: the role of ERK1/2, G2/M‐phase cell cycle arrest and p53 expression

Lee

Park²,

et al. 2010

Phytotherapy Research

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The thorns of Gleditsia sinensis are used as a medicinal herb in China and Korea. However, the mechanisms responsible for the antitumor effects of the water extract of Gleditsia sinensis thorns (WEGS) remain unknown. HCT116 cells treated with the WEGS at a dose of 800 μg/mL (IC₅₀) showed a significant decrease in cell growth and an increase in cell cycle arrest during the G2/M-phase. G2/M-phase arrest was correlated with increased p53 levels and down-regulation of the check-point proteins, cyclinB1, Cdc2 and Cdc25c. In addition, treatment with WEGS induced phosphorylation of extracellular signal-regulated kinase (ERK), p38 MAP kinase and JNK (c-Jun N-terminal kinases). Moreover, inhibition of ERK by treatment of cells with the ERK-specific inhibitor PD98059 blocked WEGS-mediated p53 expression. Similarly, blockage of ERK function in the WEGS-treated cells reversed cell-growth inhibition and decreased cell cycle proteins. Finally, in vivo WEGS treatment significantly inhibited the growth of HCT116 tumor cell xenografts in nude mice with no negative side effects, including loss of body weight. These results describe the molecular mechanisms whereby the WEGS might inhibit proliferation of colon cancer both in vitro and in vivo, suggesting that WEGS has potential as an anticancer agent for the treatment of malignancies.

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“…85) Asymmetric allylic amination can be a useful tool in the enantioselective total synthesis of nitrogen-containing natural products. Our catalytic asymmetric reaction was successfully applied to the first enantioselective total synthesis of tangutorine (76), which exhibits cytotoxic activity against human colon cancer HT-29 cells [86][87][88][89][90][91] (Fig. 6).…”

Section: Trivalent Ir and Pentavalent Ir Speciesmentioning

confidence: 98%

Development of New Methods in Organic Synthesis and Their Applications to the Synthesis of Biologically Interesting Natural Products

Hamada

2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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2,6-Dimethyl-9-Aryl-9-phosphabicyclo[3.3.1]nonanes (9-PBN and 9-NapBN) and the chiral diaminophosphine oxides (DIAPHOXs) derived from aspartic acid have been introduced as useful ligands and preligands, respectively, for transition metal-catalyzed asymmetric synthesis. anti-Selective asymmetric hydrogenation of α-amino-β-ketoesters using Ru-, Rh-, Ir-, and Ni-catalysts through dynamic kinetic resolution have been developed for the first time, producing efficiently important anti β-hydroxy-α-amino acids. The total synthesis of several biologically active natural products was achieved by use of the transition metal-catalyzed reaction using DIAPHOX, anti-selective asymmetric hydrogenation, and reactions developed by us. Synthesis of tangutorine, an antitumor indole alkaloid, has been enantioselectively achieved for the first time. Enantioselective synthesis of a martinelline chiral core was accomplished using the asymmetric tandem Michael-Aldol reaction as a key step developed by us. This synthesis represents the formal total synthesis of martinelline and martinellic acid. Papuamide B was synthesized through the elucidation of unknown stereostructures by using the anti-selective asymmetric hydrogenation and reactions developed by us.

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Tangutorine induces p21 expression and abnormal mitosis in human colon cancer HT-29 cells

Cited by 38 publications

References 43 publications

Regulation of p21, MMP-1, and MDR-1 Expression in Human Colon Carcinoma HT29 Cells by Tian Xian Liquid, a Chinese Medicinal Formula, In Vitro and In Vivo

Regulation of p21, MMP-1, and MDR-1 Expression in Human Colon Carcinoma HT29 Cells by Tian Xian Liquid, a Chinese Medicinal Formula, In Vitro and In Vivo

Gleditsia sinensis thorn extract inhibits human colon cancer cells: the role of ERK1/2, G2/M‐phase cell cycle arrest and p53 expression

Development of New Methods in Organic Synthesis and Their Applications to the Synthesis of Biologically Interesting Natural Products

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