The natural cytokinin 2OH3MeOBAR induces cell death by a mechanism that is different from that of the „classical“ cytokinin ribosides

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F17%3A00476457" target="_blank" >RIV/61389030:_____/17:00476457 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15110/17:73584794 RIV/61989592:15310/17:73584794

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.phytochem.2017.01.004" target="_blank" >http://dx.doi.org/10.1016/j.phytochem.2017.01.004</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.phytochem.2017.01.004" target="_blank" >10.1016/j.phytochem.2017.01.004</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The natural cytokinin 2OH3MeOBAR induces cell death by a mechanism that is different from that of the „classical“ cytokinin ribosides

Popis výsledku v původním jazyce

Cytokinin ribosides (N-6-substituted adenosines) have demonstrated anticancer activity in various cultured cell lines, several xenografts and even a small clinical trial. Effects of kinetin riboside, N-6-benzyladenosine (BAR) and N-6-isopentenyladenosine on various parameters related to apoptosis have also been reported, but not directly compared with those of the highly active naturally occurring aromatic cytokinins oTR (ortho-topolin riboside) and 2OH3MeOBAR (N-6-(2-hydroxy-3-methoxybenzyl) adenosine). Here we show that 2OH3MeOBAR is the most active cytokinin riboside studied to date (median, 1st quartile, 3rd quartile and range of GI50 in tests with the NCI60 cell panel: 0.19, 0.10, 0.43 and 0.02 to 15.7 mu M respectively) and it differs from other cytokinins by inducing cell death without causing pronounced ATP depletion. Analysis of NCI60 test data suggests that its activity is independent of p53 status. Further we demonstrate that its 5'-monophosphate, the dominant cancer cell metabolite, inhibits the candidate oncogene DNPH1. Synthesis, purification, HPLC-MS identification and HPLC-UV quantification of 2OH3MeOBAR metabolites are also reported.

Název v anglickém jazyce

The natural cytokinin 2OH3MeOBAR induces cell death by a mechanism that is different from that of the „classical“ cytokinin ribosides

Popis výsledku anglicky

Cytokinin ribosides (N-6-substituted adenosines) have demonstrated anticancer activity in various cultured cell lines, several xenografts and even a small clinical trial. Effects of kinetin riboside, N-6-benzyladenosine (BAR) and N-6-isopentenyladenosine on various parameters related to apoptosis have also been reported, but not directly compared with those of the highly active naturally occurring aromatic cytokinins oTR (ortho-topolin riboside) and 2OH3MeOBAR (N-6-(2-hydroxy-3-methoxybenzyl) adenosine). Here we show that 2OH3MeOBAR is the most active cytokinin riboside studied to date (median, 1st quartile, 3rd quartile and range of GI50 in tests with the NCI60 cell panel: 0.19, 0.10, 0.43 and 0.02 to 15.7 mu M respectively) and it differs from other cytokinins by inducing cell death without causing pronounced ATP depletion. Analysis of NCI60 test data suggests that its activity is independent of p53 status. Further we demonstrate that its 5'-monophosphate, the dominant cancer cell metabolite, inhibits the candidate oncogene DNPH1. Synthesis, purification, HPLC-MS identification and HPLC-UV quantification of 2OH3MeOBAR metabolites are also reported.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10611 - Plant sciences, botany

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Phytochemistry

ISSN

0031-9422

e-ISSN

—

Svazek periodika

136

Číslo periodika v rámci svazku

APR

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

156-164

Kód UT WoS článku

000397354700019

EID výsledku v databázi Scopus

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