Skip to main content
SpringerLink
Log in

Plant Hormone Cytokinins for Modulating Human Aging and Age-Related Diseases

  • Chapter
  • First Online:
Hormones in Ageing and Longevity

Part of the book series: Healthy Ageing and Longevity ((HAL,volume 6))

Abstract

Cytokinins are phytohormones that regulate plant growth, development and senescence. Experiments both in vitro and in vivo demonstrate that they can also have diverse effects on animal cells and tissues. Particularly interesting is their ability to protect cells against various forms of stress and prevent some detrimental effects of cell aging. For example, human skin fibroblasts cultured in the presence of kinetin or trans-zeatin retain some characteristics of cells of lower passage. Kinetin is even able to increase the lifespan of invertebrates. In this chapter, we review protective effects of cytokinins in animals at molecular, cellular, tissue and organismal levels. We also discuss potential application of cytokinins for the treatment of age-related diseases, including neurodegenerations, inflammatory diseases and disorders caused by aberrant cell proliferation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ADK:

Adenosine kinase

A2AR:

A2A adenosine receptor

A3R:

A3R adenosine receptor

BA:

N 6-benzyladenine

BAR:

N 6-benzyladenosine

ENT:

Equilibrative nucleoside transporter

tZ:

trans-zeatin

tZR:

trans-zeatin riboside

iP:

N 6-isopentenyladenine

iPR:

N 6-isopentenyladenosine

ipt:

Isopentenyltransferase

K:

Kinetin

KR:

Kinetin riboside

KRTP:

Kinetin riboside-5′-triphosphate

oTR:

ortho-topolin riboside

pTR:

para-topolin riboside

ROS:

Reactive oxygen species

References

  • Amiable C, Pochet S, Padilla A, Labesse G, Kaminski PA (2013) N6-substituted AMPs inhibit mammalian deoxynucleotide N-hydrolase DNPH1. PLoS ONE 8:e80755. doi:10.1371/journal.pone.0080755

    Article  PubMed  PubMed Central  Google Scholar 

  • Barciszewski J, Siboska GE, Pedersen BO, Clark BFC, Rattan SIS (1996) Evidence for the presence of kinetin in DNA and cell extracts. FEBS 393:197–200

    Article  CAS  Google Scholar 

  • Barciszewski J, Siboska GE, Pedersen BO, Clark BFC, Rattan SIS (1997) A mechanism for the in vivo formation of N6-furfuryladenine, kinetin, as a secondary oxidative damage product of DNA. FEBS Lett 414:457–460. doi:10.1016/S0014-5793(97)01037-5

    Article  CAS  PubMed  Google Scholar 

  • Barciszewski J, Mielcarek M, Stobiecki M, Siboska G, Clark BFC (2000) Identification of 6-furfuryladenine (kinetin) in human urine. Biochem Biophys Res Commun 279:69–73. doi:10.1006/bbrc.2000.3928

    Article  CAS  PubMed  Google Scholar 

  • Berge U, Kristensen P, Rattan SIS (2006) Kinetin-induced differentiation of normal human keratinocytes undergoing aging in vitro. Ann NY Acad Sci 1067:332–336. doi:10.1196/annals.1354.045

    Article  CAS  PubMed  Google Scholar 

  • Berge U, Kristensen P, Rattan SIS (2008) Hormetic modulation of differentiation of normal human epidermal keratinocytes undergoing replicative senescence in vitro. Exp Gerontol 43:658–662. doi:10.1016/j.exger.2007.12.009

    Article  CAS  PubMed  Google Scholar 

  • Bifulco M, D’Alessandro A, Paladino S, Malfitano AM, Notarnicola M, Caruso MG, Laezza C (2013) N6-isopentenyladenosine improves nuclear shape in fibroblasts from humans with progeroid syndromes by inhibiting the farnesylation of prelamin A. FEBS J 280:6223–6232. doi:10.1111/febs.12544

    Article  CAS  PubMed  Google Scholar 

  • Blad CC, von Frijtag Drabbe Künzel JK, de Vries H, Mulder-Krieger T, Bar-Yehuda S, Fishman P, Ijzerman AP (2011) Putative role of the adenosine A(3) receptor in the antiproliferative action of N (6)-(2-isopentenyl)adenosine. Purinergic Signal 7:453–462. doi:10.1007/s11302-011-9244-9

  • Borea PA, Varani K, Vincenzi F, Baraldi PG, Tabrizi MA, Merighi S, Gessi S (2014) The A3 adenosine receptor: history and perspectives. Pharmacol Rev 67:74–102. doi:10.1124/pr.113.008540

    Article  CAS  Google Scholar 

  • Brizzolari A, Marinello C, Carini M, Santaniello E, Biondi PA (2016) Evaluation of the antioxidant activity and capacity of some natural N6-substituted adenine derivatives (cytokinins) by fluorimetric and spectrophotometric assays. J Chromatogr B: Anal Technol Biomed Life Sci 1019:164–168. doi:10.1016/j.jchromb.2015.12.047

    Article  CAS  Google Scholar 

  • Bruns DR, Drake JC, Biela LM, Peelor FF, Miller BF, Hamilton KL (2015) Nrf2 signaling and the slowed aging phenotype: evidence from long-lived models. Oxid Med Cell Longev 2015:1–15. doi:10.1155/2015/732596

    Article  Google Scholar 

  • Cabello CM, Bair WB 3rd, Ley S, Lamore SD, Azimian S, Wondrak GT (2009) The experimental chemotherapeutic N6-furfuryladenosine (kinetin-riboside) induces rapid ATP depletion, genotoxic stress, and CDKN1A(p21) upregulation in human cancer cell lines. Biochem Pharmacol 77:1125–1138. doi:10.1016/j.bcp.2008.12.002

    Article  CAS  PubMed  Google Scholar 

  • Carimi F, Zottini M, Formentin E, Terzi M, Lo Schiavo F (2003) Cytokinins: new apoptotic inducers in plants. Planta 216:413–421. doi:10.1007/s00425-002-0862-x

    CAS  PubMed  Google Scholar 

  • Chen C, Kristopeit SM (1981) Metabolism of cytokinin: deribosylation of cytokinin ribonucleoside by adenosine nucleosidase from wheat germ cells. Plant Physiol 68:1020–1023. doi:10.1104/pp.68.5.1020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheong J, Goh D, Yong JWH, Tan SN, Ong ES (2009) Inhibitory effect of kinetin riboside in human heptamoa, HepG2. Mol BioSyst 5:91–98. doi:10.1039/b712807j

    Article  CAS  PubMed  Google Scholar 

  • Chhabra P, Linden J, Lobo P, Okusa MD, Brayman KL (2012) The immunosuppressive role of adenosine A2A receptors in ischemia reperfusion injury and islet transplantation. Curr Diabetes Rev 8:419–433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chheda G, Mittelman A (1972) N6-(Δ2-isopentenyl) adenosine metabolism in man. Biochem Pharmacol 21:27–37

    Article  CAS  PubMed  Google Scholar 

  • Chiu P-C, Chan C-C, Lin H-M, Chiu H-C (2007) The clinical anti-aging effects of topical kinetin and niacinamide in Asians: a randomized, double-blind, placebo-controlled, split-face comparative trial. J Cosmet Dermatol 6:243–249. doi:10.1111/j.1473-2165.2007.00342.x

    Article  PubMed  Google Scholar 

  • Chiu F-L, Lin J-T, Chuang C-Y, Chien T, Chen C-M, Chen K-H, Hsiao H-Y, Lin Y-S, Chern Y, Kuo H-C (2015) Elucidating the role of the A2A adenosine receptor in neurodegeneration using neurons derived from Huntington’s disease iPSCs. Hum Mol Genet 24:6066–6079. doi:10.1093/hmg/ddv318

    Article  CAS  PubMed  Google Scholar 

  • Choi SJ, Jeong C-H, Choi S-G, Chun J-Y, Kim YJ, Lee J, Shin D-H, Heo HJ (2009) Zeatin prevents amyloid beta-induced neurotoxicity and scopolamine-induced cognitive deficits. J Med Food 12:271–277. doi:10.1089/jmf.2007.0678

    Article  CAS  PubMed  Google Scholar 

  • Chou S-Y, Lee Y-C, Chen H-M, Chiang M-C, Lai H-L, Chang H-H, Wu Y-C, Sun C-N, Chien C-L, Lin Y-S, Wang S-C, Tung Y-Y, Chang C, Chern Y (2005) CGS21680 attenuates symptoms of Huntington’s disease in a transgenic mouse model. J Neurochem 93:310–320. doi:10.1111/j.1471-4159.2005.03029.x

    Article  CAS  PubMed  Google Scholar 

  • Ciaglia E, Pisanti S, Picardi P, Laezza C, Sosa S, Tubaro A, Vitale M, Gazzerro P, Malfitano AM, Bifulco M (2014) N6-isopentenyladenosine affects cytotoxic activity and cytokines production by IL-2 activated NK cells and exerts topical anti-inflammatory activity in mice. Pharmacol Res 89:1–10. doi:10.1016/j.phrs.2014.07.003

    Article  CAS  PubMed  Google Scholar 

  • Ciaglia E, Abate M, Laezza C, Pisanti S, Vitale M, Seneca V, Torelli G, Franceschelli S, Catapano G, Gazzerro P, Bifulco M (2016) Antiglioma effects of N6-isopentenyladenosine, an endogenous isoprenoid end product, through the downregulation of epidermal growth factor receptor. Int J Cancer. doi:10.1002/ijc.30505

    PubMed  Google Scholar 

  • Colombo F, Falvella FS, De Cecco L, Tortoreto M, Pratesi G, Ciuffreda P, Ottria R, Santaniello E, Cicatiello L, Weisz A, Dragani TA (2009) Pharmacogenomics and analogues of the antitumour agent N6-isopentenyladenosine. Int J Cancer 124:2179–2185. doi:10.1002/ijc.24168

    Article  CAS  PubMed  Google Scholar 

  • Dassano A, Mancuso M, Giardullo P, De Cecco L, Ciuffreda P, Santaniello E, Saran A, Dragani TA, Colombo F (2014) N(6)-isopentenyladenosine and analogs activate the NRF2-mediated antioxidant response. Redox Biol 2:580–589. doi:10.1016/j.redox.2014.03.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • David M, Gospodinov DK, Gheorghe N, Mateev GS, Rusinova MV, Hristakieva E, Solovastru LG, Patel RV, Giurcaneanu C, Hitova MC, Purcaru AI, Horia B, Tsingov II, Yankova RK, Kadurina MI, Ramon M, Rotaru M, Simionescu O, Benea V, Demerdjieva ZV, Cosgarea MR, Morariu HS, Michael Z, Cristodor P, Nica C, Silverman MH, Bristol DR, Harpaz Z, Farbstein M, Cohen S, Fishman P (2016) Treatment of plaque-type psoriasis with oral CF101: data from a phase II/III multicenter, randomized, controlled trial. J Drugs Dermatol 15:931–938

    PubMed  Google Scholar 

  • Doležal K, Popa I, Hauserová E, Spíchal L, Chakrabarty K, Novák O, Kryštof V, Voller J, Holub J, Strnad M (2007) Preparation, biological activity and endogenous occurrence of N6-benzyladenosines. Bioorg Med Chem 15:3737–3747. doi:10.1016/j.bmc.2007.03.038

    Article  PubMed  CAS  Google Scholar 

  • Gan S, Amasino RM (1995) Inhibition of leaf senescence by autoregulated production of cytokinin. Science 270:1986–1988. doi:10.1126/science.270.5244.1986

  • Ge L, Yong JWH, Tan SN, Yang XH, Ong ES (2004) Analysis of some cytokinins in coconut (Cocos nucifera L.) water by micellar electrokinetic capillary chromatography after solid-phase extraction. J Chromatogr A 1048:119–126

    Article  CAS  PubMed  Google Scholar 

  • Gillissen B, Burkle L, Andre B, Kuhn C, Rentsch D, Brandl B, Frommer WB (2000) A new family of high-affinity transporters for adenine, cytosine, and purine derivatives in Arabidopsis. Plant Cell 12:291–300. doi:10.1105/tpc.12.2.291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldstein S, Czapski G (1991) SOD-like activity studies of cytokinin-copper(II) complexes. Free Radic Res Commun 12–13(Pt 1):173–177. doi:10.3109/10715769109145783

    Article  Google Scholar 

  • Griffaut B, Bos R, Maurizis J-CC, Madelmont J-CC, Ledoigt G (2004) Cytotoxic effects of kinetin riboside on mouse, human and plant tumour cells. Int J Biol Macromol 34:271–275. doi:10.1016/j.ijbiomac.2004.06.004

    Article  CAS  PubMed  Google Scholar 

  • Haider S, Tabassum S, Perveen T (2016) Scopolamine-induced greater alterations in neurochemical profile and increased oxidative stress demonstrated a better model of dementia: a comparative study. Brain Res Bull 127:234–247. doi:10.1016/j.brainresbull.2016.10.002

    Article  CAS  PubMed  Google Scholar 

  • Havlíček L, Hanuš J, Veselý J, Leclerc S, Meijer L, Shaw G, Strnad M (1997) Cytokinin-derived cyclizn-dependent kinase inhibitors: synthesis and cdc2 inhibitory activity of olomoucine and related compounds. J Med Chem 40:408–412. doi:10.1021/jm960666x

    Article  PubMed  Google Scholar 

  • Heo H-J, Hong S-C, Cho H-Y, Hong B, Kim H-K, Kim E-K, Shin D-H (2002) Inhibitory effect of zeatin, isolated from Fiatoua villosa, on acetylcholinesterase activity from PC12 cells. Mol Cells 13:113–117

    CAS  PubMed  Google Scholar 

  • Hertz NT, Berthet A, Sos ML, Thorn KS, Burlingame AL, Nakamura K, Shokat KM (2013) A neo-substrate that amplifies catalytic activity of Parkinson’s-disease-related kinase PINK1. Cell 154:737–747. doi:10.1016/j.cell.2013.07.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirose N, Takei K, Kuroha T, Kamada-Nobusada T, Hayashi H, Sakakibara H (2008) Regulation of cytokinin biosynthesis, compartmentalization and translocation. J Exp Bot 59:75–83. doi:10.1093/jxb/erm157

    Article  CAS  PubMed  Google Scholar 

  • Horgan R, Hewett EW, Horgan JM, Purse J, Wareing PF (1975) A new cytokinin from Populus x robusta. Phytochemistry 14:1005–1008. doi:10.1016/0031-9422(75)85176-4

    Article  CAS  Google Scholar 

  • Hsiao G, Shen M-Y, Lin K-H, Chou C-Y, Tzu N-H, Lin C-H, Chou D-S, Chen T-F, Sheu J-R (2003) Inhibitory activity of kinetin on free radical formation of activated platelets in vitro and on thrombus formation in vivo. Eur J Pharmacol 465:281–287. doi:10.1016/S0014-2999(03)01528-0

    Article  CAS  PubMed  Google Scholar 

  • Huang C-L, Yang J-M, Wang K-C, Lee Y-C, Lin Y-L, Yang Y-C, Huang N-K (2011a) Gastrodia elata prevents huntingtin aggregations through activation of the adenosine A2A receptor and ubiquitin proteasome system. J Ethnopharmacol 138:162–168. doi:10.1016/j.jep.2011.08.075

    Article  PubMed  Google Scholar 

  • Huang N-K, Lin J-H, Lin J-T, Lin C-I, Liu EM, Lin C-J, Chen W-P, Shen Y-C, Chen H-M, Chen J-B, Lai H-L, Yang C-W, Chiang M-C, Wu Y-S, Chang C, Chen J-F, Fang J-M, Lin Y-L, Chern Y (2011b) A new drug design targeting the adenosinergic system for Huntington’s disease. PLoS ONE 6:e20934. doi:10.1371/journal.pone.0020934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ishii Y, Hori Y, Sakai S, Honma Y (2002) Control of differentiation and apoptosis of human myeloid leukemia cells by cytokinins and cytokinin nucleosides, plant redifferentiation-inducing hormones. Cell Growth Differ 13:19–26

    CAS  PubMed  Google Scholar 

  • Ishii Y, Kasukabe T, Honma Y (2005a) Induction of CCAAT/enhancer binding protein-δ by cytokinins, but not by retinoic acid, during granulocytic differentiation of human myeloid leukaemia cells. Br J Haematol 128:540–547. doi:10.1111/j.1365-2141.2004.05326.x

    Article  CAS  PubMed  Google Scholar 

  • Ishii Y, Kasukabe T, Honma Y (2005b) Immediate up-regulation of the calcium-binding protein S100P and its involvement in the cytokinin-induced differentiation of human myeloid leukemia cells. Biochim Biophys Acta Mol Cell Res 1745:156–165. doi:10.1016/j.bbamcr.2005.01.005

    Article  CAS  Google Scholar 

  • Ji C, Yang Y, Yang B, Xia J, Sun W, Su Z, Yu L, Shan S, He S, Cheng L, Wan Y, Bi Z (2010) Trans-Zeatin attenuates ultraviolet induced down-regulation of aquaporin-3 in cultured human skin keratinocytes. Int J Mol Med 26:257–263. doi:10.3892/ijmm-00000460

    CAS  PubMed  Google Scholar 

  • Jones KR, Kang EM (2015) Graft versus host disease: new insights into A2A receptor agonist therapy. Comput Struct Biotechnol J 13:101–105. doi:10.1016/j.csbj.2014.12.003

    Article  CAS  PubMed  Google Scholar 

  • Jorda R, Paruch K, Krystof V (2012) Cyclin-dependent kinase inhibitors inspired by roscovitine: purine bioisosteres. Curr Pharm Des 18:2974–2980

    Article  CAS  PubMed  Google Scholar 

  • Kim S, Lee JJ, Jung E, Lee JJ, Huh S, Hwang H, Kim Y, Park D (2009) 6-Benzylaminopurine stimulates melanogenesis via cAMP-independent activation of protein kinase A. Arch Dermatol Res 301:253–258. doi:10.1007/s00403-008-0924-4

    Article  CAS  PubMed  Google Scholar 

  • Kimura T, Doi K (2004) Depigmentation and rejuvenation effects of kinetin on the aged skin of hairless descendants of Mexican hairless dogs. Rejuvenation Res 7:32–39. doi:10.1089/154916804323105062

    Article  CAS  PubMed  Google Scholar 

  • Kryštof V, Lenobel R, Havlíček L, Kuzma M, Strnad M (2002) Synthesis and biological activity of olomoucine II. Bioorg Med Chem Lett 12:3283–3286

    Article  PubMed  Google Scholar 

  • Kudo T, Kiba T, Sakakibara H (2010) Metabolism and long-distance translocation of cytokinins. J Integr Plant Biol 52:53–60. doi:10.1111/j.1744-7909.2010.00898.x

    Article  CAS  PubMed  Google Scholar 

  • Kurakawa T, Ueda N, Maekawa M, Kobayashi K, Kojima M, Nagato Y, Sakakibara H, Kyozuka J (2007) Direct control of shoot meristem activity by a cytokinin-activating enzyme. Nature 445:652–655. doi:10.1038/nature05504

    Article  CAS  PubMed  Google Scholar 

  • Laezza C, Notarnicola M, Caruso MG, Messa C, Macchia M, Bertini S, Minutolo F, Portella G, Fiorentino L, Stingo S, Bifulco M (2006) N6-isopentenyladenosine arrests tumor cell proliferation by inhibiting farnesyl diphosphate synthase and protein prenylation. FASEB J Off Publ Fed Am Soc Exp Biol 20:412–418. doi:10.1096/fj.05-4044lsf

    CAS  Google Scholar 

  • Laezza C, Caruso MG, Gentile T, Notarnicola M, Malfitano AM, Di Matola T, Messa C, Gazzerro P, Bifulco M (2009) N6-isopentenyladenosine inhibits cell proliferation and induces apoptosis in a human colon cancer cell line DLD1. Int J Cancer 124:1322–1329. doi:10.1002/ijc.24056

    Article  CAS  PubMed  Google Scholar 

  • Laezza C, Malfitano AM, Di Matola T, Ricchi P, Bifulco M (2010) Involvement of Akt/NF-κB pathway in N6-isopentenyladenosine-induced apoptosis in human breast cancer cells. Mol Carcinog 49:892–901. doi:10.1002/mc.20666

    Article  CAS  PubMed  Google Scholar 

  • Lappas CM (2015) The plant hormone zeatin riboside inhibits T lymphocyte activity via adenosine A2A receptor activation. Cell Mol Immunol 12:107–112. doi:10.1038/cmi.2014.33

    Article  CAS  PubMed  Google Scholar 

  • Lee Y-C, Yang Y-C, Huang C-L, Kuo T-Y, Lin J-H, Yang D-M, Huang N-K (2012) When cytokinin, a plant hormone, meets the adenosine A2A receptor: a novel neuroprotectant and lead for treating neurodegenerative disorders? PLoS ONE 7:e38865. doi:10.1371/journal.pone.0038865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Y, Zhang Z, Yang X (2011) Kinetin protects against lipid peroxidation and improves antioxidant status in cultured astrocytes and mouse brain exposed to d-galactose. Afric J Biotech 10:11721–11727. doi:10.5897/AJB11.289

    CAS  Google Scholar 

  • Luo C, Yi B, Tao G, Li M, Chen Z, Tang W, Zhang JH, Feng H (2010) Adenosine A3 receptor agonist reduces early brain injury in subarachnoid haemorrhage. NeuroReport 21:892–896. doi:10.1097/WNR.0b013e32833dbd13

    Article  CAS  PubMed  Google Scholar 

  • Madeo F, Zimmermann A, Maiuri MC, Kroemer G (2015) Essential role for autophagy in life span extension. J Clin Invest 125:85–93. doi:10.1172/JCI73946

    Article  PubMed  PubMed Central  Google Scholar 

  • Maria Pugliese A, Coppi E, Volpini R, Cristalli G, Corradetti R, Jeong LS, Jacobson KA, Pedata F (2007) Role of adenosine A3 receptors on CA1 hippocampal neurotransmission during oxygen–glucose deprivation episodes of different duration. Biochem Pharmacol 74:768–779. doi:10.1016/j.bcp.2007.06.003

    Article  CAS  Google Scholar 

  • McClintock D, Ratner D, Lokuge M, Owens DM, Gordon LB, Collins FS, Djabali K (2007) The mutant form of lamin A that causes Hutchinson-Gilford progeria is a biomarker of cellular aging in human skin. PLoS ONE 2:e1269. doi:10.1371/journal.pone.0001269

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • McCullough JL, Weinstein GW (2002) Clinical study of safety and efficacy of using topical kinetin 0.10% (Kinerase) to treat photodamaged skin. Cosmet Dermatol 15(9):29–32

    Google Scholar 

  • McCullough JL, Garcia RL, Reece B (2008) A clinical study of topical Pyratine 6 for improving the appearance of photodamaged skin. J Drugs Dermatol JDD 7:131–135

    PubMed  Google Scholar 

  • McCullough JL, Weinstein GW (2002) Clinical study to assess the safety and efficacy of topical kinetin 0.10% (Kinerase®) for photodamaged skin. Cosmet Dermatol 15:29–32

    Google Scholar 

  • McDaniel DH, Neudecker BA, DiNardo JC, Lewis JA 2nd, Maibach HI (2005) Idebenone: a new antioxidant—Part I. Relative assessment of oxidative stress protection capacity compared to commonly known antioxidants. J Cosmet Dermatol 4:10–17. doi:10.1111/j.1473-2165.2005.00152.x

    Article  CAS  PubMed  Google Scholar 

  • Mcdermott SP, Eppert K, Notta F, Isaac M, Datti A, Al-awar R, Minden MD, Dick JE, Dc W, Wrana J (2012) A small molecule screening strategy with validation on human leukemia stem cells uncovers the therapeutic efficacy of kinetin riboside A small molecule screening strategy with validation on human leukemia stem cells uncovers the therapeutic efficacy of ki. Blood 119:1200–1207. doi:10.1182/blood-2011-01-330019

    Article  CAS  PubMed  Google Scholar 

  • Meisel H, Günther S, Martin D, Schlimme E (1998) Apoptosis induced by modified ribonucleosides in human cell culture systems. FEBS Lett 433:265–268

    Article  CAS  PubMed  Google Scholar 

  • Milne GR, Palmer TM (2011) Anti-inflammatory and immunosuppressive effects of the A2A adenosine receptor. Sci World J 11:320–339. doi:10.1100/tsw.2011.22

    Article  CAS  Google Scholar 

  • Mittelman A, Evans JT, Chheda GB (1975) Cytokinins as chemotherapeutic agents. Ann NY Acad Sci 255:225–234

    Article  CAS  PubMed  Google Scholar 

  • Mlejnek P, Doležel P (2005) Apoptosis induced by N6-substituted derivatives of adenosine is related to intracellular accumulation of corresponding mononucleotides in HL-60 cells. Toxicol In Vitro 19:985–990. doi:10.1016/j.tiv.2005.06.023

    Article  CAS  PubMed  Google Scholar 

  • Mlejnek P, Kuglík P (2000) Induction of apoptosis in HL-60 cells by N6-benzyladenosine. J Cell Biochem 77:6–17. doi:10.1002/(SICI)1097-4644(20000401)77:1<6:AID-JCB2>3.0.CO;2-3

    Article  CAS  PubMed  Google Scholar 

  • Mlejnek P, Procházka S (2002) Activation of caspase-like proteases and induction of apoptosis by isopentenyladenosine in tobacco BY-2 cells. Planta 215:158–166. doi:10.1007/s00425-002-0733-5

    Article  CAS  PubMed  Google Scholar 

  • Mok DWS, Mok MC (2001) Cytokinin metabolism and action. Annu Rev Plant Physiol Plant Mol Biol 52:89–118

    Article  CAS  PubMed  Google Scholar 

  • Olsen A, Siboska GE, Clark BF, Rattan SI (1999) N(6)-Furfuryladenine, kinetin, protects against Fenton reaction-mediated oxidative damage to DNA. Biochem Biophys Res Commun 265:499–502. doi:10.1006/bbrc.1999.1669

    Article  CAS  PubMed  Google Scholar 

  • Ortiz A, Elkeeb L, Truitt A, Hindiyeh R, Aquino L, Tran M, Weinstein G (2009) Topical PRK 124 (0.125%) lotion for improving the signs and symptoms of rosacea. J Drugs Dermatol JDD 8:459–462

    PubMed  Google Scholar 

  • Ottria R, Casati S, Maier JAM, Mariotti M, Ciuffreda P (2009) Novel isopentenyladenosine analogues: synthesis, characterization, and evaluation of antiproliferative activity on bladder carcinoma cells. nucleosides, nucleotides and nucleic acids 28:736–751. doi:10.1080/15257770903155550

  • Pisanti S, Picardi P, Ciaglia E, Margarucci L, Ronca R, Giacomini A, Malfitano AM, Casapullo A, Laezza C, Gazzerro P, Bifulco M (2014) Antiangiogenic effects of N6-isopentenyladenosine, an endogenous isoprenoid end product, mediated by AMPK activation. FASEB J 28:1132–1144. doi:10.1096/fj.13-238238

    Article  CAS  PubMed  Google Scholar 

  • Rajabi M, Gorincioi E, Santaniello E (2012) Antiproliferative activity of kinetin riboside on HCT-15 colon cancer cell line. Nucleosides Nucleotides Nucleic Acids 31:474–481. doi:10.1080/15257770.2012.681825

    Article  CAS  PubMed  Google Scholar 

  • Rattan SI, Clark BF (1994) Kinetin delays the onset of ageing characteristics in human fibroblasts. Biochem Biophys Res Commun 201:665–672

    Article  CAS  PubMed  Google Scholar 

  • Rattan SIS, Sodagam L (2005) Gerontomodulatory and youth-preserving effects of zeatin on human skin fibroblasts undergoing aging in vitro. Rejuvenation Res 8:46–57. doi:10.1089/rej.2005.8.46

    Article  CAS  PubMed  Google Scholar 

  • Sharma SP, Kaur P, Rattan SI (1995) Plant growth hormone kinetin delays ageing, prolongs the lifespan and slows down development of the fruitfly Zaprionus paravittiger. Biochem Biophys Res Commun 216:1067–1071. doi:10.1006/bbrc.1995.2729

    Article  CAS  PubMed  Google Scholar 

  • Sharma SP, Kaur J, Rattan SI (1997) Increased longevity of kinetin-fed Zaprionus fruitflies is accompanied by their reduced fecundity and enhanced catalase activity. Biochem Mol Biol Int 41:869–875. doi:10.1080/15216549700201911

    CAS  PubMed  Google Scholar 

  • Skoog F, Strong FM, Miller CO (1965) Cytokinins. Science 148:532–533. doi:10.1126/science.148.3669.532-a

    Article  CAS  PubMed  Google Scholar 

  • Slaugenhaupt SA, Mull J, Leyne M, Cuajungco MP, Gill SP, Hims MM, Quintero F, Axelrod FB, Gusella JF (2004) Rescue of a human mRNA splicing defect by the plant cytokinin kinetin. Hum Mol Genet 13:429–436. doi:10.1093/hmg/ddh046

    Article  CAS  PubMed  Google Scholar 

  • Spíchal L, Rakova NY, Riefler M, Mizuno T, Romanov GA, Strnad M, Schmülling T (2004) Two cytokinin receptors of Arabidopsis thaliana, CRE1/AHK4 and AHK3, differ in their ligand specificity in a bacterial assay. Plant Cell Physiol 45:1299–1305. doi:10.1093/pcp/pch132

    Article  PubMed  Google Scholar 

  • Spinola M, Colombo F, Falvella FS, Dragani TA (2007) N6-isopentenyladenosine: a potential therapeutic agent for a variety of epithelial cancers. Int J Cancer 120:2744–2748. doi:10.1002/ijc.22601

    Article  CAS  PubMed  Google Scholar 

  • Štarha P, Trávníček Z, Herchel R, Popa I, Suchý P, Vančo J (2009) Dinuclear copper(II) complexes containing 6-(benzylamino)purines as bridging ligands: synthesis, characterization, and in vitro and in vivo antioxidant activities. J Inorg Biochem 103:432–440. doi:10.1016/j.jinorgbio.2008.12.009

    Article  PubMed  CAS  Google Scholar 

  • Strnad M (1997) The aromatic cytokinins. Physiol Plant 101:674–688. doi:10.1111/j.1399-3054.1997.tb01052.x

    Article  CAS  Google Scholar 

  • Tiedemann RE, Mao X, Shi C-X, Zhu YX, Palmer SE, Sebag M, Marler R, Chesi M, Fonseca R, Bergsagel PL, Schimmer AD, Stewart AK (2008) Identification of kinetin riboside as a repressor of CCND1 and CCND2 with preclinical antimyeloma activity. J Clin Invest 118:1750–1764. doi:10.1172/JCI34149

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tournas JA, Lin F-H, Burch JA, Selim MA, Monteiro-Riviere NA, Zielinski JE, Pinnell SR (2006) Ubiquinone, idebenone, and kinetin provide ineffective photoprotection to skin when compared to a topical antioxidant combination of vitamins C and E with ferulic acid. J Invest Dermatol 126:1185–1187. doi:10.1038/sj.jid.5700232

    Article  CAS  PubMed  Google Scholar 

  • Tremaine AM, Ortiz A, Elkeeb L, Tran M, Weinstein G (2010) Long-term efficacy and safety of topical PRK 124 (0.125%) lotion (Pyratine-XR) in the treatment of mild-to-moderate rosacea. J drugs dermatology JDD 9:647–650

    PubMed  Google Scholar 

  • van der Hoeven D, Gizewski ET, Auchampach JA (2010) Activation of the A3 adenosine receptor inhibits fMLP-induced Rac activation in mouse bone marrow neutrophils. Biochem Pharmacol 79:1667–1673. doi:10.1016/j.bcp.2010.02.002

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Verbeke P, Siboska GE, Clark BF, Rattan SI (2000) Kinetin inhibits protein oxidation and glycoxidation in vitro. Biochem Biophys Res Commun 276:1265–1270. doi:10.1006/bbrc.2000.3616

    Article  CAS  PubMed  Google Scholar 

  • Vermeulen K, Strnad M, Kryštof V, Havlíček L, Van der Aa A, Lenjou M, Nijs G, Rodrigus I, Stockman B, van Onckelen H, Van Bockstaele DR, Berneman ZN (2002) Antiproliferative effect of plant cytokinin analogues with an inhibitory activity on cyclin-dependent kinases. Leuk Off J Leuk Soc Am Leuk Res Fund UK 16:299–305. doi:10.1038/sj.leu.2402378

    Article  CAS  Google Scholar 

  • Veselý J, Havlíček L, Strnad M, Blow JJ, Donella-Deana A, Pinna L, Letham DS, Kato J, Detivaud L, Leclerc S (1994) Inhibition of cyclin-dependent kinases by purine analogues. Eur J Biochem 224:771–786. doi:10.1111/j.1432-1033.1994.00771.x

    Article  PubMed  Google Scholar 

  • Vičanová J, Bouez C, Lacroix S, Lindmark L, Damour O (2006) Epidermal and dermal characteristics in skin equivalent after systemic and topical application of skin care ingredients. Ann NY Acad Sci 1067:337–342. doi:10.1196/annals.1354.046

    Article  PubMed  CAS  Google Scholar 

  • Voller J, Zatloukal M, Lenobel R, Doležal K, Béres T, Kryštof V, Spíchal L, Niemann P, Džubák P, Hajdúch M, Strnad M (2010) Anticancer activity of natural cytokinins: a structure-activity relationship study. Phytochemistry 71:1350–1359. doi:10.1016/j.phytochem.2010.04.018

    Article  CAS  PubMed  Google Scholar 

  • Voller J, Béres T, Zatloukal M, Kaminski PA, Niemann P, Doležal K, Džubák P, Hajdúch M, Strnad M (2017) The natural cytokinin 2OH3MeOBAR induces cell death by a mechanism that is different from that of the “classical” cytokinin ribosides. Phytochemistry. doi:10.1016/j.phytochem.2017.01.004

    Google Scholar 

  • Walla J, Szücová L, Císařová I, Gucký T, Zatloukal M, Doležal K, Greplová J, Massino FJ, Strnad M (2010) X-ray structure, NMR and stability-in-solution study of 6-(furfurylamino)-9-(tetrahydropyran-2-yl)purine—a new active compound for cosmetology. J Mol Struct 975(1–3):376–380

    Article  CAS  Google Scholar 

  • Wang L, Sun C, Wang Z-H, Guo G-Q (2012) Mechanism of apoptotosis induced by ortho-topolin riboside in human hepatoma cell line SMMC-7721. Food Chem Toxicol 50:1962–1968. doi:10.1016/j.fct.2012.03.053

    Article  CAS  PubMed  Google Scholar 

  • Wanitphakdeedecha R, Meeprathom W, Manuskiatti W (2015) Efficacy and safety of 0.1% kinetin cream in the treatment of photoaging skin. Indian J Dermatol Venereol Leprol 81:547. doi:10.4103/0378-6323.157446

    Article  PubMed  Google Scholar 

  • Werner T, Schmülling T (2009) Cytokinin action in plant development. Curr Opin Plant Biol 12(5):527–538. doi:10.1016/j.pbi.2009.07.002

  • Wu JJ, Weinstein GD, Kricorian GJ, Kormeili T, McCullough JL (2007) Topical kinetin 0.1% lotion for improving the signs and symptoms of rosacea. Clin Exp Dermatol 32:693–695. doi:10.1111/j.1365-2230.2007.02513.x

    Article  CAS  PubMed  Google Scholar 

  • Yang B, Ji C, Kang J, Chen W, Bi Z, Wan Y (2009) Trans-zeatin inhibits UVB-induced matrix metalloproteinase-1 expression via MAP kinase signaling in human skin fibroblasts. Int J Mol Med 23:555–560

    Article  CAS  PubMed  Google Scholar 

  • Zhang K, Novak O, Wei Z, Gou M, Zhang X, Yu Y, Yang H, Cai Y, Strnad M, Liu C-J (2014) Arabidopsis ABCG14 protein controls the acropetal translocation of root-synthesized cytokinins. Nat Commun 5:3274. doi:10.1038/ncomms4274

    PubMed  Google Scholar 

  • Zwack PJ, Rashotte AM (2013) Cytokinin inhibition of leaf senescence. Plant Signal Behav 8:e24737. doi:10.4161/psb.24737

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

The study was partly supported by the Internal Grant Agency of Palacký University (IGA_PrF_2017_013), Endowment Fund of Palacký University and by the Grant Agency of the Czech Republic (7-14007S). This work was also funded by the Ministry of Education, Youth and Sports of the Czech Republic (the National Program for Sustainability I: Nr. LO1204).

The authors also would like to thank Sees-editing Ltd. (UK) for the English editing of this manuscript.

Author information

Authors and Affiliations

  1. Laboratory of Growth Regulators, Centre of the Region Haná for Biotechnological and Agricultural Research, Institute of Experimental Botany ASCR, Palacký University, Šlechtitelů 27, 78371, Olomouc, Czech Republic

    Jiří Voller, Barbara Maková, Alena Kadlecová, Gabriel Gonzalez & Miroslav Strnad

Authors
  1. Jiří Voller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Barbara Maková
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alena Kadlecová
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gabriel Gonzalez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Miroslav Strnad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jiří Voller .

Editor information

Editors and Affiliations

  1. Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark

    Suresh Rattan

  2. Department of Biochemistry, North Eastern Hill University, Shillong, Megalaya, India

    Ramesh Sharma

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Voller, J., Maková, B., Kadlecová, A., Gonzalez, G., Strnad, M. (2017). Plant Hormone Cytokinins for Modulating Human Aging and Age-Related Diseases. In: Rattan, S., Sharma, R. (eds) Hormones in Ageing and Longevity. Healthy Ageing and Longevity, vol 6. Springer, Cham. https://doi.org/10.1007/978-3-319-63001-4_14

Download citation

Publish with us

Policies and ethics

Search

Navigation