The polar neutral and basic taxoids isolated from needles and twigs of Taxus cuspidata and their biological activity

Wang, Liyan; Bai, Liming; Tokunaga, Daisuke; Watanabe, Yusuke; Hasegawa, Toshiaki; Sakai, Jun‐ichi; Tang, Wanxia; Bai, Yuhua; Hirose, Katsutoshi; Yamori, Takao; Tomida, Akihiro; Tsuruo, Takashi; Ando, Masayoshi

doi:10.1007/s10086-008-0964-6

Cited by 10 publications

(6 citation statements)

References 41 publications

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“…The side effects of anticancer agents are a serious problem in cancer chemotherapy and an effective anticancer approach with potent activity and minimal side effects is highly desirable [ 15 ]. It is well known that some of the side effects of 5-FU are gastrointestinal such as nausea, vomiting, and myelosuppression.…”

Section: Discussionmentioning

confidence: 99%

Anticancer activity of an extract from needles and twigs of Taxus cuspidata and its synergistic effect as a cocktail with 5-fluorouracil

Shang

Qiao

et al. 2011

BMC Complement Altern Med

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BackgroundBotanical medicines are increasingly combined with chemotherapeutics as anticancer drug cocktails. This study aimed to assess the chemotherapeutic potential of an extract of Taxus cuspidata (TC) needles and twigs produced by artificial cuttage and its co-effects as a cocktail with 5-fluorouracil (5-FU).MethodsComponents of TC extract were identified by HPLC fingerprinting. Cytotoxicity analysis was performed by MTT assay or ATP assay. Apoptosis studies were analyzed by H & E, PI, TUNEL staining, as well as Annexin V/PI assay. Cell cycle analysis was performed by flow cytometry. 5-FU concentrations in rat plasma were determined by HPLC and the pharmacokinetic parameters were estimated using 3p87 software. Synergistic efficacy was subjected to median effect analysis with the mutually nonexclusive model using Calcusyn1 software. The significance of differences between values was estimated by using a one-way ANOVA.ResultsTC extract reached inhibition rates of 70-90% in different human cancer cell lines (HL-60, BGC-823, KB, Bel-7402, and HeLa) but only 5-7% in normal mouse T/B lymphocytes, demonstrating the broad-spectrum anticancer activity and low toxicity to normal cells of TC extract in vitro. TC extract inhibited cancer cell growth by inducing apoptosis and G2/M cell cycle arrest. Most interestingly, TC extract and 5-FU, combined as a cocktail, synergistically inhibited the growth of cancer cells in vitro, with Combination Index values (CI) ranging from 0.90 to 0.26 at different effect levels from IC50 to IC90 in MCF-7 cells, CI ranging from 0.93 to 0.13 for IC40 to IC90 in PC-3M-1E8 cells, and CI < 1 in A549 cells. In addition, the cocktail had lower cytotoxicity in normal human cell (HEL) than 5-FU used alone. Furthermore, TC extract did not affect the pharmacokinetics of 5-FU in rats.ConclusionsThe combinational use of the TC extract with 5-FU displays strong cytotoxic synergy in cancer cells and low cytotoxicity in normal cells. These findings suggest that this cocktail may have a potential role in cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Anticancer activity of an extract from needles and twigs of Taxus cuspidata and its synergistic effect as a cocktail with 5-fluorouracil

Shang

Qiao

et al. 2011

BMC Complement Altern Med

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“…This effort resulted in the identification of more than 350 taxane diterpenoids from these yew trees, expanding the diterpenoid family, which continues to grow in size [ 19 ]. However, direct isolation from natural sources is limited due to the slow growth of yew trees, their limited numbers in nature, as well as very high costs, and strict national forest protection policies [ 20 ]. This has consequently sparked interest in active exploration for new taxane drugs using natural taxanes as starting materials for synthesis and its modifications, biotransformation employing Ginkgo , and Platycodon grandiflorus cell suspension cultures [ 19 ].…”

Section: Resultsmentioning

confidence: 99%

TaxKB: a knowledge base for new taxane-related drug discovery

et al. 2015

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BackgroundTaxanes are naturally occurring compounds which belong to a powerful group of chemotherapeutic drugs with anticancer properties. Their current use, clinical efficacy, and unique mechanism of action indicate their potentiality for cancer drug discovery and development thereby promising to reduce the high economy associated with cancer worldwide. Extensive research has been carried out on taxanes with the aim to combat issues of drug resistance, side effects, limited natural supply, and also to increase the therapeutic index of these molecules. These efforts have led to the isolation of many naturally occurring compounds belonging to this family (more than 350 different kinds), and the synthesis of semisynthetic analogs of the naturally existing molecules (>500), and has also led to the characterization of many (>1000) of them. A web-based database system on clinically exploitable taxanes, providing a link between the structure and the pharmacological property of these molecules could help to reduce the druggability gap for these molecules.ResultsTaxane knowledge base (TaxKB, http://bioinfo.au-kbc.org.in/taxane/Taxkb/), is an online multi-tier relational database that currently holds data on 42 parameters of 250 natural and 503 semisynthetic analogs of taxanes. This database provides researchers with much-needed information necessary for drug development. TaxKB enables the user to search data on the structure, drug-likeness, and physicochemical properties of both natural and synthetic taxanes with a “General Search” option in addition to a “Parameter Specific Search.” It displays 2D structure and allows the user to download the 3D structure (a PDB file) of taxanes that can be viewed with any molecular visualization tool. The ultimate aim of TaxKB is to provide information on Absorption, Distribution, Metabolism, and Excretion/Toxicity (ADME/T) as well as data on bioavailability and target interaction properties of candidate anticancer taxanes, ahead of expensive clinical trials.ConclusionThis first web-based single-information portal will play a central role and help researchers to move forward in taxane-based cancer drug research.

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“…The polar neutral taxoids 7-epitaxol (269) and 7-epicephalomannine (270) displayed a strong cytotoxicity against VA-13 cells with an IC 50 of 0.0063 and 0.024 mg mL 21 , respectively. 116 Taxezopidine M (271 * ) reduced CaCl 2induced microtubule polymerization at a higher concentration of 50 mM. 117 on phenylepherine-induced vasoconstriction with rate 27-41% at the concentration 10 mM.…”

Section: Sesquiterpenoidsmentioning

confidence: 99%

Bioactive constituents from toxic seed plants in China

et al. 2013

RSC Adv.

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Toxic plants, regarded as unusual natural resources, are important sources for novel bioactive chemical entities and even new clinical drugs, and are receiving increasing attention. The present review summarizes more than 550 constituents with considerable bioactivities from about 120 toxic seed plant species in the last fifteen years (1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012), as well as follow-up studies on structural modification, SAR and action mechanisms, building on the foundations of the first monograph ''Toxic plants in China'' edited by Chen and Zheng in 1987. A thorough study on bioactive constituents from toxic plants could benefit proper utilization and improve the therapeutic index. It is hoped to lay an available foundation for future drug research and development. On the other hand, bioactive constituents could be used as probes to discover new targets and explore the mysteries of organisms.

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The polar neutral and basic taxoids isolated from needles and twigs of Taxus cuspidata and their biological activity

Cited by 10 publications

References 41 publications

Anticancer activity of an extract from needles and twigs of Taxus cuspidata and its synergistic effect as a cocktail with 5-fluorouracil

Anticancer activity of an extract from needles and twigs of Taxus cuspidata and its synergistic effect as a cocktail with 5-fluorouracil

TaxKB: a knowledge base for new taxane-related drug discovery

Bioactive constituents from toxic seed plants in China

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