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

Voller, Jiří; Béres, Tibor; Zatloukal, Marek; Kaminski, P.A.; Niemann, Percy; Doležal, Karel; Džubák, Petr; Hajdúch, Marián; Strnad, Miroslav

doi:10.1016/j.phytochem.2017.01.004

Cited by 15 publications

(19 citation statements)

References 28 publications

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“…It appears that the HeLa cells can avoid the cytotoxicity of BAR by an alternative mechanism through which BAR is converted into the FB form, BA, instead of the nucleotide form, BARP. This finding is unique to this study and is contrary to what has previously been documented in mammalian cells treated with CKs . Interestingly, a large increase in the concentration of iPRP within the BAR‐treated cell pellets was observed compared to the untreated HeLa pellets.…”

Section: Discussioncontrasting

confidence: 98%

“…Given the cytotoxic nature of the riboside fraction, it was expected that the 10 −6 mol/L concentration would be the most likely to induce cytotoxicity; however, this effect was not observed. As previously mentioned, apoptosis induced by various N 6 compounds is related to the intracellular phosphorylation of those compounds and activation of caspases . Unlike previous studies, the nucleotide fraction of BAR, BARP, was not the dominant metabolite following treatment with BAP.…”

Section: Discussioncontrasting

confidence: 56%

“…A, Observed benzyladenine metabolism demonstrating the structural derivatives (nucleotide, N6‐benzyladenine‐9‐riboside‐5′ (either mono‐, di‐, or tri‐) phosphate; riboside (BARP), benzyladenine riboside (BAR); free base (FB), and benzyladenine (BA) detected in the treated HeLa culture supernatants and the proposed enzymes responsible for the interconversions between cytokinin (CK) structural forms. This information was inferred from this study and other in vitro mammalian cell culture investigations . Numbers represent inferred enzymes as follows: 1. adenosine kinase (EC 2.7.1.20); 2. purine nucleotide phosphorylase (EC 2.4.2.1); 3. adenine phophoribosyltransferase (EC 2.4.2.1).…”

Section: Resultsmentioning

confidence: 99%

“…CKs have been gaining much attention in mammalian studies, mostly for their potential therapeutic roles as anticancer agents when applied exogenously to in vitro cell cultures . Much emphasis has been placed on documenting novel CKs that exert cytotoxicity on a wide range of mammalian cancer cell lines . Through these studies, it is evident that the structural derivatives of the CK are essential to their specific anticancer activity—with the Rs fractions exerting the most cytotoxic effects.…”

Section: Introductionmentioning

confidence: 99%

“…29,30 Much emphasis has been placed on documenting novel CKs that exert cytotoxicity on a wide range of mammalian cancer cell lines. 30,31 Through these studies, it is evident that the structural derivatives of the CK are essential to their specific anticancer activity-with the Rs fractions exerting the most cytotoxic effects. While insight into the roles of CKs in mammalian cells is gained through these studies, much remains to be understood about the in vivo metabolism and function of endogenous mammalian CKs.…”

Section: Introductionmentioning

confidence: 99%

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Phytohormone metabolism in human cells: Cytokinins are taken up and interconverted in HeLa cell culture

et al. 2019

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Cytokinins (CKs) encompass a group of phytohormones, known to orchestrate many critical processes in plant development. Excluding Archaea, CKs are pervasive among all kingdoms, but much less is reported about their metabolism beyond plants. Recent evidence from mammalian tissues indicates the presence of six additional CK forms beyond the previously identified, single mammalian CK, N6‐isopentenyladenosine (i6A). There is limited understanding of CK biosynthesis pathways in mammalian systems; therefore, human cervical cancer (HeLa) cells were used to further characterize CK processing by tracking the interconversion of CKs into their various structural derivatives in mammalian cells in a time‐course study. Through high‐performance liquid chromatography‐positive electrospray ionization‐tandem mass spectrometry (HPLC‐(+ESI)‐MS/MS), we document changes in the functional profiles of endogenous CKs in a human cell line following metabolism by HeLa cell cultures. The nucleotide CK fraction (iPRP) was found exclusively within the cell pellet (0.34 pmol/106 cells), and the active free base (FB) form (iP) and riboside fraction (iPR) were found in greater abundance extracellularly (1.67 and 0.10 nmol/L respectively). For further confirmation, we demonstrate that HeLa cells metabolize an exogenously supplied CK, N6‐benzyladenosine (BAR). In the HeLa culture supernatant, a 12‐fold decrease in BAR concentration was observed within the first 24 hours of incubation accompanied by a fivefold increase in the FB form, N6‐benzyladenine (BA). These findings support the hypothesis that HeLa cells have the enzymatic pathways required for the metabolism of both endogenous and exogenous CKs.

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Section: Discussioncontrasting

confidence: 98%

Section: Discussioncontrasting

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%