Preparation and biological activity of 6-benzylaminopurine derivatives in plants and human cancer cells

Doležal, Karel; Popa, Igor; Kryštof, Vladimír; Spíchal, Lukáš; Fojtíková, Martina; Holub, Jan; Lenobel, René; Schmülling, Thomas; Strnad, Miroslav

doi:10.1016/j.bmc.2005.09.004

Cited by 118 publications

(68 citation statements)

References 34 publications

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“…There is also clear discrimination of aromatic and isoprenoid cytokinins at the receptor level (Spı´chal et al, 2004). The interaction of aromatic cytokinins with cellular signaling systems also appears to be different to that of isoprenoid cytokinins (Dolezˇal et al, 2006(Dolezˇal et al, , 2007. Only four aromatic cytokinins were detected in the two seaweed species analysed in this study with benzyladenosine (BAR) occurring at relatively high concentrations in both species (Table 1).…”

Section: Discussionmentioning

confidence: 87%

Endogenous cytokinins, auxins and abscisic acid inUlva fasciata(Chlorophyta) andDictyota humifusa(Phaeophyta): towards understanding their biosynthesis and homoeostasis

Stirk

Novák

Hradecká

et al. 2009

European Journal of Phycology

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Hormones are present in seaweeds, but little is known about their biosynthesis and regulation. The aim of this study was to investigate variation in concentration and composition of endogenous cytokinins, auxins and abscisic acid in two seaweeds collected over a 1 year period to gain a more complete picture of the types of hormones present during a range of environmental and developmental conditions. Ulva fasciata (Ulvales, Chlorophyta) and Dictyota humifusa (Dictyotales, Phaeophyta) were collected bimonthly from the inter-tidal zone at Rocky Bay, South Africa. Ethanol extracts of the samples containing a mixture of internal standards were purified using a combined DEAE-Sephadex-octadecylsilica column, followed by immuno-affinity chromatography and analysed by high-performance liquid chromatography -mass spectrometry to quantify different cytokinins, auxins and abscisic acid. cis-Zeatin, isopentenyladenine and their ribotide and riboside conjugates were the main cytokinins present in both U. fasciata and D. humifusa with low concentrations of trans-zeatin, dihydrozeatin and aromatic cytokinins. Very low concentrations of O-glucosides and riboside-O-glucosides and no N-glucosides were detected in any of the samples. Based on the cytokinins detected, we propose that as in higher plants, the ribotides are also the first intermediates formed during de novo biosynthesis in seaweeds and are subsequently converted to free-bases and ribosides. The only indole compounds detected in both species were free indole-3-acetic acid and indole-3-acetamide (IAM), suggesting that IAM is the intermediate in auxin biosynthesis. Endogenous abscisic acid was detected in most samples with levels in U. fasciata generally being higher than those measured in D. humifusa.

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Section: Discussionmentioning

confidence: 87%

Endogenous cytokinins, auxins and abscisic acid inUlva fasciata(Chlorophyta) andDictyota humifusa(Phaeophyta): towards understanding their biosynthesis and homoeostasis

Stirk

Novák

Hradecká

et al. 2009

European Journal of Phycology

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“…Ishii et al (2002) reported that various types of cytokinins or cytokinin ribosides inhibit the proliferation of HL-60 cells, followed by differentiation into normal granulocytes or apoptosis. Together with the abovementioned report by Dolezel et al (2006), that cytokinins reduce the activity of CDK-like histone kinase in Arabidopsis, it may be said that the antiproliferative effects of cytokinins in plant and animal cells may be mediated by similar mechanisms related to regulation of CDK activity. In future studies, the effect of cytokinins on CDK activity in plants and animals must be considered in detail.…”

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confidence: 75%

“…An important question for future studies is how benzyladenine inhibits G1 progression after 0 or 4 h of treatment. Dolezel et al (2006) reported that CDK-like histone kinase activity was reduced in vitro by high concentrations (Ͼ50 mM) of benzyladenine and isopentenyladenine using protein kinases purified from Arabidopsis callus; therefore, the effects of benzyladenine on CDKs or other cell cycleregulating factors must be considered.…”

Section: Discussionmentioning

confidence: 99%

Benzyladenine arrests cell cycle progression in G1 phase in tobacco BY-2 cells preceding induction of cell death

Suda

Iwai

Satoh

et al. 2009

Plant Biotechnology

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Micromolar concentrations of exogenously applied cytokinins can inhibit the growth of tobacco BY-2 (Nicotiana tabacum L. cv. Bright Yellow 2) cells and induce cell death. To determine whether the antiproliferative and cell death-inducing mechanisms of cytokinins are linked, we investigated the inhibition of cell cycle transition by the cytokinin benzyladenine using BY-2 cells. Mitotic index and flow cytometric analyses revealed that benzyladenine decreased the rate of cells entering the G2 and M phases a few hours after treatment of unsynchronized cells. Additionally, for cells synchronized in M phase, benzyladenine delayed (at 10 mM) or arrested (at 50 mM) cell cycle progression at G1. Expression patterns of cell cycle-related genes (PCNA and A3-, A1-and B1-type cyclins) also indicated G1 arrest by a 50 mM benzyladenine treatment at the M or G1 phase. Cell cycle arrest was detected prior to the induction of cell death by the treatment. Increase in number of dead cells was observed 16 h after each treatment at M or G1, suggesting that cell death may not be induced when cells reach a specific time point in G1 phase but, rather, in a time-dependent manner following benzyladenine treatment.Key words: Cell cycle, cytokinin, Nicotiana tabacum BY-2 cells, programmed cell death, synchronous culture.Plant Biotechnology 26, 225-235 (2009) Original PaperAbbreviations: DAPI, 4Ј,6-diamidino-2-phenylindole; DMSO, dimethyl sulfoxide; FAM-Asp-Glu-Val-Asp-FMK, fluoromethyl ketone peptide inhibitor of caspase-3/7; FLICA, fluorochrome inhibitor of caspase; G1, gap 1; G2, gap 2; M, mitosis; NO, nitric oxide; PCD, programmed cell death; ROS, reactive oxygen species; S, synthesis. This article can be found at http://www.jspcmb.jp/ Evidence also suggests that cytokinins induce cell death in plants via biochemical pathways involving the activation of caspase-like proteases, production of reactive oxygen species (ROS) or nitric oxide (NO), release of cytochrome c from mitochondria, and upregulation of Bax inhibitor-1 expression and cytosolic Ca 2ϩ fluxes, which are similar to those of animal apoptosis. Therefore, cytokinin-mediated cell death is considered to be a programmed cell death (PCD) with conserved pathways in plants and animals, which is also observed after stress treatments such as heat shock (Vacca et al. 2004(Vacca et al. , 2006 or hydrogen peroxide (Houot et al. 2001). However, the pathways through which cytokinins induce cell death are mostly unknown. Moreover, there remains one problem that whether the antiproliferative mechanism, which seems to occur simultaneously with the cell death, is correlated to the induction of cell death.Recent studies have suggested that the cell cycle regulates the induction of cell death. Oxidative stress mediated by menadione slows DNA replication and delays cellular entry into mitosis by inhibiting the G1 to S phase transition, and a high concentration of menadione induces cell death in tobacco BY-2 cells (Reichheld et al. 1999). Ethylene treatment increases BY-2 cell mortalit...

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“…The precursors (2,6-dichloro-9-isopropylpurine, 2,4-dihydroxybenzylamine hydroiodide, and 2,5-dihydroxybenzylamine hydrochloride) re-quired for synthesizing the possible olomoucine II metabolites were prepared as described previously (Otyepka et al, 2000;Dolezal et al, 2006Dolezal et al, , 2007. The appropriate dihydroxybenzylamine isomers (1 mmol) for the metabolites were then added individually, together with triethylamine (6 mmol), to a suspension of 2,6-dichloro-9-isopropylpurine (1 mmol) in ethyl acetate.…”

Section: Methodsmentioning

confidence: 99%

Interactions of Olomoucine II with Human Liver Microsomal Cytochromes P450

Siller

Anzenbacher²,

Anzenbacherová³

et al. 2009

Drug Metab Dispos

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ABSTRACT:Olomoucine II is a cyclin-dependent kinase inhibitor and a potential antineoplastic agent because it can arrest animal cell cycles. This study examines its interactions with human liver microsomal cytochrome P450 (P450) enzymes. Spectroscopic and high-performance liquid chromatography (HPLC) methods were used to estimate the degree of olomoucine II-mediated inhibition of enzymatic activities of eight drug-metabolizing P450s in vitro. In addition, mass spectrometry coupled with HPLC was used to identify an olomoucine II metabolite (2,5-dihydroxyroscovitine) formed in the reaction mixtures, and CYP3A4 was found to be responsible for the hydroxylation of the N 6 -benzyl ring at position 5, leading to this compound. Olomoucine II significantly inhibited the enzymatic activities of CYP1A2, CYP2C9, and (to a lesser degree) CYP3A4. The results indicate that use of olomoucine II as a drug could affect the activities of CYP3A4, CYP1A2, and CYP2C9 in vivo. Hence, the clinical relevance of these interactions should be carefully evaluated.

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Preparation and biological activity of 6-benzylaminopurine derivatives in plants and human cancer cells

Cited by 118 publications

References 34 publications

Endogenous cytokinins, auxins and abscisic acid inUlva fasciata(Chlorophyta) andDictyota humifusa(Phaeophyta): towards understanding their biosynthesis and homoeostasis

Endogenous cytokinins, auxins and abscisic acid inUlva fasciata(Chlorophyta) andDictyota humifusa(Phaeophyta): towards understanding their biosynthesis and homoeostasis

Benzyladenine arrests cell cycle progression in G1 phase in tobacco BY-2 cells preceding induction of cell death

Interactions of Olomoucine II with Human Liver Microsomal Cytochromes P450

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