Cytotoxic effects of kinetin riboside on mouse, human and plant tumour cells

Griffaut, B.; Bos, Romain; Maurizis, Jean‐Claude; Madelmont, Jean‐Claude; Ledoigt, Gérard

doi:10.1016/j.ijbiomac.2004.06.004

Cited by 39 publications

(29 citation statements)

References 24 publications

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“…Kinetin riboside is toxic at the dose of 25 mg/kg. It was also shown to have a cytotoxic effect on plant crown-gall cells [61]. Kinetin and other cytokinins induce the granulocytic differentiation of human myeloid leukemia HL-60 cells.…”

Section: Kinetin Propertiesmentioning

confidence: 99%

Kinetin—A multiactive molecule

Barciszewski

Massino²,

Clark

2007

International Journal of Biological Macromolecules

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Section: Kinetin Propertiesmentioning

confidence: 99%

Kinetin—A multiactive molecule

Barciszewski

Massino²,

Clark

2007

International Journal of Biological Macromolecules

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“…In plants, cytokinins control many aspects of plant development (19,20) and also induce apoptosis of plant tumor cells (38) as well as regulating cell division. Others have recently investigated the differentiating activities of plant cytokinins against human cancers (38)(39)(40) and have noted growth inhibition that may in part be accounted for by suppression of cyclin Ds. In addition, several cytokinins, including kinetin riboside, have been shown to cause alterations in mitochondrial membrane potential as a prelude to apoptosis (40).…”

Section: Figurementioning

confidence: 99%

Identification of kinetin riboside as a repressor of CCND1 and CCND2 with preclinical antimyeloma activity

Tiedemann¹,

Mao²,

Shi³

et al. 2008

J. Clin. Invest.

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Knockout and transgenic studies in mice demonstrate that normal somatic tissues redundantly express 3 cyclin D proteins, whereas tumor cells seem dependent on a single overexpressed cyclin D. Thus, selective suppression of the individual cyclin D deregulated in a tumor represents a biologically valid approach to targeted cancer therapy. In multiple myeloma, overexpression of 1 of the cyclin D proteins is a ubiquitous feature, unifying at least 7 different initiating genetic events. We demonstrate here that RNAi of genes encoding cyclin D1 and cyclin D2 (CCND1 and CCND2, respectively) inhibits proliferation and is progressively cytotoxic in human myeloma cells. By screening a chemical library using a cell-based assay for inhibition of CCND2 trans-activation, we identified the plant cytokinin kinetin riboside as an inhibitor of CCND2 trans-activation. Kinetin riboside induced marked suppression of CCND2 transcription and rapidly suppressed cyclin D1 and D2 protein expression in primary myeloma cells and tumor lines, causing cell-cycle arrest, tumor cell-selective apoptosis, and inhibition of myeloma growth in xenografted mice. Mechanistically, kinetin riboside upregulated expression of transcription repressor isoforms of cAMP-response element modulator (CREM) and blocked both trans-activation of CCND2 by various myeloma oncogenes and cis-activation of translocated CCND1, suggesting induction of an overriding repressor activity that blocks multiple oncogenic pathways targeting cyclin D genes. These data support targeted repression of cyclin D genes as a therapeutic strategy for human malignancies. IntroductionMultiple myeloma (MM) is a postgerminal center B cell malignancy characterized by clonal plasma cell expansion. The disease manifests clinically with anemia, monoclonal immunoglobulin, renal insufficiency, and lytic bone lesions and currently affects 63,000 people in the United States alone (1); moreover, as it is currently incurable, MM causes a disproportionate 2% of all cancer deaths.Although myeloma tumors present with complex karyotypes and an assortment of structural and numerical chromosomal abnormalities, these tumors are unified in their ubiquitous targeting of cyclin D genes for overexpression. Of MM tumors, 54% overexpress cyclin D1 (CCND1), 48% overexpress cyclin D2 (CCND2), 3% overexpress cyclin D3 (CCND3), and 8% overexpress both CCND1 and CCND2 (2). Deregulated expression of single CCND genes in MM occurs as the result of selective cyclin D gene trans-activation by deregulated transcription factors or from translocation of a single

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“…The same biocatalyst was employed for the synthesis of 9-( -D-arabinofuranosyl)adenine (19) using readily accessible by chemical method ara-C [50] and adenine as substrates [41] (Scheme 6), and N 6 -benzyladenosine (isolated yield 61%) by the D-ribofuranose transfer from uridine to N 6 -benzyladenine [40]. Recently, cytokinin nucleosides and, in particular, kinetin and N 6 -benzyladenine ribosides, attracted attention owing to their strong cytotoxic effects on human tumor cells [45], potent inhibition of growth of human myeloid leukemia HL-60 cells and induction of apoptosis [46]. Moreover, base halogenated derivatives of N 6 -benzyladenine as well as sugar modified derivatives of cytokinines represent very important family of agonists and antagonists for adenosine receptors and are under intense investigation [47].…”

Section: Biotechnological Synthesis Of Nucleo-sides Nucleoside Phosphmentioning

confidence: 99%

Biotechnology of Nucleic Acid Constituents - State of the Art and Perspectives

Mikhailopulo

2007

COC

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A survey of the chemo-enzymatic methodology for the preparation of nucleosides of biological importance is presented. The emphasis is made on the enzymatic transglycosylation and glycosylation employing the nucleoside phosphorylases and N-deoxyribosyltransferases. Application of the whole cells as biocatalysts as well as purified enzymes from wild-type bacteria and recombinant enzymes is considered.

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Cytotoxic effects of kinetin riboside on mouse, human and plant tumour cells

Cited by 39 publications

References 24 publications

Kinetin—A multiactive molecule

Kinetin—A multiactive molecule

Identification of kinetin riboside as a repressor of CCND1 and CCND2 with preclinical antimyeloma activity

Biotechnology of Nucleic Acid Constituents - State of the Art and Perspectives

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