Effects of kinetin riboside on proliferation and proapoptotic activities in human normal and cancer cell lines

Dudzik, Paulina; Dulińska-Litewka, Joanna; Wyszko, Eliza; Jędrychowska, Patrycja; Opałka, Maciej; Barciszewski, Jan; Laidler, Piotr

doi:10.1002/jcb.23132

Cited by 21 publications

(11 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The plant hormone cytokinins are adenine derivatives with an isoprenoid or an aromatic side chain substituted at the N6 position. For instance, N 6 -isopentenyladenosine, N 6 -furfuryladenosine (kinetin riboside) and N 6 -benzyladenosine have cytotoxic effects for different human cell lines derived from solid tumours [ 3 – 10 ]. These compounds also show good efficiency in vivo using several animal and xenograft models of cancer [ 4 , 5 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

N6-Substituted AMPs Inhibit Mammalian Deoxynucleotide N-Hydrolase DNPH1

et al. 2013

View full text Add to dashboard Cite

The gene dnph1 (or rcl) encodes a hydrolase that cleaves the 2’-deoxyribonucleoside 5’-monophosphate (dNMP) N-glycosidic bond to yield a free nucleobase and 2-deoxyribose 5-phosphate. Recently, the crystal structure of rat DNPH1, a potential target for anti-cancer therapies, suggested that various analogs of AMP may inhibit this enzyme. From this result, we asked whether N 6-substituted AMPs, and among them, cytotoxic cytokinin riboside 5’-monophosphates, may inhibit DNPH1. Here, we characterized the structural and thermodynamic aspects of the interactions of these various analogs with DNPH1. Our results indicate that DNPH1 is inhibited by cytotoxic cytokinins at concentrations that inhibit cell growth.

show abstract

Section: Introductionmentioning

confidence: 99%

N6-Substituted AMPs Inhibit Mammalian Deoxynucleotide N-Hydrolase DNPH1

et al. 2013

View full text Add to dashboard Cite

show abstract

“…KR has also been reported as a potent inhibitor of CCND2 whose transactivation leads to the downregulation of cyclins D1 and D2 [36]. These effects seem to be selective and promote cell death in cancer cells [38]. KR and several purine derivatives that are widely used in cancer treatment have a specific and unique mode of action, which may involve the activation of a cellular response to stress and maintenance of the metabolic balance of the cells [24].…”

Section: Discussionmentioning

confidence: 99%

Circumventing the Crabtree effect: forcing oxidative phosphorylation (OXPHOS) via galactose medium increases sensitivity of HepG2 cells to the purine derivative kinetin riboside

et al. 2020

Self Cite

View full text Add to dashboard Cite

Small-molecule compound-based therapies have provided new insights into cancer treatment against mitochondrial impairment. N6-furfuryladenosine (kinetin riboside, KR) is a purine derivative and an anticancer agent that selectively affects the molecular pathways crucial for cell growth and apoptosis by interfering with mitochondrial functions and thus might be a potential mitotoxicant. Metabolism of cancer cells is predominantly based on the Crabtree effect that relies on glucose-induced inhibition of cell respiration and thus on oxidative phosphorylation (OXPHOS), which supports the survival of cancer cells in metabolic stress conditions. The simplest way to circumvent this phenomenon is to replace glucose with galactose in the culture environment. Consequently, cells become more sensitive to mitochondrial perturbations caused by mitotoxicants. In the present study, we evaluated several cellular parameters and investigated the effect of KR on mitochondrial functions in HepG2 cells forced to rely mainly on OXPHOS. We showed that KR in the galactose environment is a more potent apoptosis-inducing agent. KR decreases the mitochondrial membrane potential, reduces glutathione level, depletes cellular ATP, and induces reactive oxygen species (ROS) production in the OXPHOS state, leading to the loss of cell viability. Taken together, these results demonstrate that KR directly acts on the mitochondria to limit their function and that the sensitivity of cells is dependent on their ability to cope with energetic stress.

show abstract

“…2h ), a natural compound present in the coconut milk, is an anti-proliferative agent belonging to the ‘Cytokinins’ class of plant hormones. Kinetin riboside treatment results in CDKN1A upregulation, ATP depletion, cell cycle arrest at the G 2 /M phase, disruption of mitochondrial membrane potential, release of cytochrome c, caspase-3 activation, upregulation of Bad and down-regulation of Bcl-2 [ 96 – 98 ]. In vitro, Kinetin riboside induces apoptosis in the CD34 + /CD38 - AML stem cell fraction and prevents LSC engraftment in NOD/SCID mouse model while sparing HSC fractions [ 99 ].…”

Section: Natural Products For Targeting Lscsmentioning

confidence: 99%

Targeting acute myeloid leukemia stem cell signaling by natural products

2017

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is the most commonly diagnosed leukemia in adults (25%) and comprises 15–20% in children. It is a genetically heterogeneous aggressive disease characterized by the accumulation of somatically acquired genetic changes, altering self-renewal, proliferation, and differentiation of hematopoietic progenitor cells, resulting in uncontrolled clonal proliferation of malignant progenitor myeloid cells in the bone marrow, peripheral blood, and occasionally in other body tissues. Treatment with modern chemotherapy regimen (cytarabine and daunorubicin) usually achieves high remission rates, still majority of patients are found to relapse, resulting in only 40–45% overall 5 year survival in young patients and less than 10% in the elderly AML patients. The leukemia stem cells (LSCs) are characterized by their unlimited self-renewal, repopulating potential and long residence in a quiescent state of G0/G1 phase. LSCs are considered to have a pivotal role in the relapse and refractory of AML. Therefore, new therapeutic strategies to target LSCs with limited toxicity towards the normal hematopoietic population is critical for the ultimate curing of AML. Ongoing research works with natural products like parthenolide (a natural plant extract derived compound) and its derivatives, that have the ability to target multiple pathways that regulate the self-renewal, growth and survival of LSCs point to ways for a possible complete remission in AML. In this review article, we will update and discuss various natural products that can target LSCs in AML.

show abstract

Effects of kinetin riboside on proliferation and proapoptotic activities in human normal and cancer cell lines

Cited by 21 publications

References 37 publications

N6-Substituted AMPs Inhibit Mammalian Deoxynucleotide N-Hydrolase DNPH1

N6-Substituted AMPs Inhibit Mammalian Deoxynucleotide N-Hydrolase DNPH1

Circumventing the Crabtree effect: forcing oxidative phosphorylation (OXPHOS) via galactose medium increases sensitivity of HepG2 cells to the purine derivative kinetin riboside

Targeting acute myeloid leukemia stem cell signaling by natural products

Contact Info

Product

Resources

About