Anti-cancer activities of cytokinin ribosides

Voller, Jiří; Béres, Tibor; Zatloukal, Marek; Džubák, Petr; Hajdúch, Marián; Doležal, Karel; Schmülling, Thomas; Strnad, Miroslav

doi:10.1007/s11101-019-09620-4

Cited by 16 publications

(6 citation statements)

References 74 publications

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“…Additionally, viral replication was also significantly reduced in cultures pre-treated with iP and iPR up to 12 h prior to infection demonstrating the ability to prime for an antiviral response ( Figure 3 ). Considering that CK interconversion and metabolism have been observed up to 72 h following exogenous application in vitro [ 8 , 36 ], further evaluation of both pre- and post- infection applications should be conducted to establish an effective treatment window.…”

Section: Discussionmentioning

confidence: 99%

Cytokinins Reduce Viral Replication and Alter Plaque Morphology of Frog Virus 3 In Vitro

Seegobin,

Logan,

Emery

et al. 2024

Viruses

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Cytokinins (CKs) are a group of N6-substituted signaling molecules whose biosynthesis and metabolism have been documented in all kingdoms of life, including vertebrates. While their biological relevance in vertebrate systems continues to be elucidated, they have broadly been documented with therapeutic effects in exogenous applications. In this study, we evaluated the virostatic potential of four types of CKs including, N6-isopentenyladenine (iP), N6-isopentenyladenosine (iPR), N6-isopentenyladenosine-5′monophosphate (iPMP), and 2-methylthiol-N6-isopentenyladenosine (2MeSiPR) against the ranavirus type species, frog virus 3 (FV3). Following concurrent treatment and infection, iP and iPR reduced viral replication by 33.8% and 59.6%, respectively, in plaque formation assays. A decrease in viral replication was also observed when CK exposure was limited to 12 h prior to infection, where iP and iPR reduced viral replication by 31% and 23.75%, respectively. Treatment with iP and iPR was also marked by 48% and 60% decreases in viral load over 72 h, respectively, as measured in single step growth curves. Plaque morphology was altered in vitro, as iP and iPR treatment increased plaque area by 83% and 112% with lytic zone formation also becoming more prevalent in corresponding treatments. Treatment with iPMP and 2MeSiPR resulted in no effect on viral kinetics in vitro. The results of this study are the first to provide evidence of CK antiviral activity against a DNA virus and highlight the importance of their structure for therapeutic investigations.

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Section: Discussionmentioning

confidence: 99%

Cytokinins Reduce Viral Replication and Alter Plaque Morphology of Frog Virus 3 In Vitro

Seegobin,

Logan,

Emery

et al. 2024

Viruses

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“…Plant-isolated compounds [1], such as flavonoids [2][3][4] and phytohormones, as well as their synthetic analogs [5][6][7][8][9] are considered to be very promising as potential anti-cancer agents.…”

Section: Introductionmentioning

confidence: 99%

Anti-Proliferative and Cytoprotective Activity of Ethylenediurea Derivatives with Alkyl and Oxygen-containing Groups as Substituents

Oshchepkov,

Kovalenko,

Kalistratova

et al. 2024

Preprint

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Natural cytokinins are a promising group of cytoprotective and anti-tumor agents. In this research, we synthesized a set of novel cytokinin analogs with alkyl substituents at various positions of the aromatic moiety, as well as with oxygen-containing groups, and tested their antiproliferative activity in MDA-MB-231, A-375, and U-87 MG cell lines, and cytoprotective properties in H2O2 and CoCl2 models. Two amino-linked compounds were anti-proliferative with the ability to act synergistically with doxorubicin, and two carbamate-based ones were cytoprotective. According to the molecular docking data, anti-proliferation was based on the A2AR and APRT inhibition and cytoprotection on the CDK2 inhibition. The obtained results are promising for the development of novel anti-cancer therapeutics.

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“…Kinetin and N 6 ‐(isopentenyl)adenine (iP) species have drawn attention for their activity in mammalian systems; the former in Huntington's disease (Bowie et al., 2018 ), myogenesis (Mielcarek & Isalan, 2021 ), aging (Sharma et al., 1995 ), and both in cancer (Choi et al., 2008 ; Ishii et al., 2002 ; Laezza et al., 2009 ; Laezza et al., 2010 ; Voller et al., 2019 ). In C2C12 myoblasts, exogenous kinetin promotes myogenesis and glucose uptake, and functions as an antioxidant (Mielcarek & Isalan, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Profiling of adenine‐derived signaling molecules, cytokinins, in myotubes reveals fluctuations in response to lipopolysaccharide‐induced cell stress

Tobin,

Seneviratne,

Phan

et al. 2023

Physiological Reports

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Cytokinins (CTKs) are a diverse collection of evolutionarily conserved adenine‐derived signaling molecules classically studied as phytohormones; however, their roles and production have been less studied in mammalian systems. Skeletal muscles are sensitive to cellular cues such as inflammation and in response, alter their secretome to regulate the muscle stem cell and myofiber niche. Using cultured C2C12 muscle cells, we profiled CTK levels to understand (1) whether CTKs are part of the muscle secretome and (2) whether CTKs are responsive to cellular stress. To induce cellular stress, C2C12 myotubes were treated with lipopolysaccharides (LPS) for 24 h and then media and cell fractions were collected for ultra high‐performance liquid chromatography tandem mass spectrometry with electrospray ionization (UHPLC‐(ESI+)‐HRMS/MS) for metabolomics and CTK profiling. Across LPS‐treated and control cells, 11 CTKs were detected in the extracellular space while 6 were detected intracellularly. We found that muscle cells are enriched in isopentenyladenine (iP) species (from free base, riboside to nucleotide forms), and that extracellular levels are increased after LPS treatment. Our study establishes that muscle cells express various forms of CTKs, and that CTK levels are responsive to LPS‐induced cell stress, suggesting a role for CTKs in intra‐ and extracellular signaling of mammalian cells.

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Anti-cancer activities of cytokinin ribosides

Cited by 16 publications

References 74 publications

Cytokinins Reduce Viral Replication and Alter Plaque Morphology of Frog Virus 3 In Vitro

Cytokinins Reduce Viral Replication and Alter Plaque Morphology of Frog Virus 3 In Vitro

Anti-Proliferative and Cytoprotective Activity of Ethylenediurea Derivatives with Alkyl and Oxygen-containing Groups as Substituents

Profiling of adenine‐derived signaling molecules, cytokinins, in myotubes reveals fluctuations in response to lipopolysaccharide‐induced cell stress

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