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Kinetin

Common Name(s): N-(2-furanylmethyl)-1H-purin-6-amine, 6-furfurylaminopurine, Kinetin, Kinetin riboside, N6-furfuryladenine

Clinical Overview

Use

Kinetin has primarily been used topically as an antiaging preparation, although there is limited clinical information to support this use. Potential uses for oral kinetin include the treatment of genetic disorders such as familial dysautonomia and certain cancers.

Dosing

Oral kinetin has only been studied in a few clinical trials of questionable quality. Topical applications are available at 0.03% to 0.1% strengths.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Information on adverse reactions due to topical application is limited. Case reports of reactions to commercial topical preparations are lacking.

Toxicology

Information is limited.

Botany

Kinetin, initially thought to be a synthetic product, was isolated over 50 years ago as a plant hormone or cytokinin. Cytokinins function as essential growth hormones that can influence cell growth and differentiation in plant and nonplant tissues. Kinetin is found in plant cell extracts, including plant root nodules and the endosperm liquid of fresh, young coconut fruit. It has also been identified in freshly extracted DNA from human cells, human urine, and herring sperm.1

History

One of the first recognized cytokinins was a component of coconut milk, which was used as a standard additive to plant tissue cultures because of its ability to induce plant cell division (cytokinesis). Studies dating back to the mid-1950s describe the structure and synthesis of the cytokinin kinetin.1, 2

Chemistry

Cytokinins are N6-substituted adenine derivatives, categorized into 3 groups: the isoprenoid, the aromatic cytokinins, and the furfural group consisting of kinetin and kinetin riboside. Kinetin is thought to originate from furfural, a primary oxidation product of the deoxyribose in DNA. Kinetin exhibits electrochemical properties, which facilitate its measurement in biological material. A review of the chemical structure of kinetin and its associated moieties has been published.1, 2, 3

Uses and Pharmacology

Cancer

Most studies utilize the kinetin riboside because free-base cytokinins are weaker cytotoxic agents, with the ribose at N9 of the purine ring essential for activity.2 Suppression of cellular signaling, cell-cycle arrest, and induction of apoptosis have been demonstrated in vitro.2, 3, 4, 5, 6, 7

Animal data

Studies have been conducted in mice with induced melanoma and myeloma. Inhibition of the tumor growth has been demonstrated.2, 3, 4

Clinical data

Clinical studies are lacking. In vitro studies have shown efficacy of kinetin riboside against human cell cancer lines, including leukemia, melanoma and hepatoma, and breast and prostate cancers.2, 3, 5, 6

Dermatological

In vitro studies in plant and human cells, including keratinocytes, have shown that kinetin modulates cell growth. Varying concentrations of kinetin have inhibiting and modulating effects on different stages of cell development.7, 8, 9, 10, 11 Kinetin is reported to have delayed aging and prolonged the lifespan of the fruitfly.12

Animal data

Topical application of kinetin to aged skin in hairless dogs for 100 days resulted in skin rejuvenation and depigmentation.1 No photoprotection was shown by either topical kinetin 0.1% or 0.5% on pig skin patches.13

Clinical data

Quality clinical trial data are lacking. Information on the purported antiaging effects of kinetin is largely limited to company-sponsored, open-label studies, which have not been published in peer-reviewed journals. One small, open-label, sponsored clinical study in mild to moderate rosacea showed improvement in facial erythema, skin roughness, and hyperpigmentation, but there was no effect on facial inflammatory pustules. In the absence of a control group, it is difficult to attribute the results to either the kinetin or the moisturizing vehicle itself.14 A double-blind, controlled study evaluating the effect of kinetin 0.03% with niacinamide over niacinamide alone found a trend toward improvement of facial aging for the kinetin study group.15

Familial dysautonomia

Familial dysautonomia is an autosomal recessive human genetic disorder caused by faulty RNA splicing that leads to impaired development of sensory and autonomic nerves. Disease severity depends on the extent of impaired coding, and small shifts in splicing can halt disease progression and neurodegeneration. The potential for kinetin in familial dysautonomia was discovered in a screening program for neurological disorders and stroke, and a proposed mechanism of action has been described.16, 17, 18

Animal data

Studies in rodents have been undertaken to evaluate the distribution of orally administered kinetin.18, 19

Clinical data

Clinical trials are limited and have been primarily conducted to elucidate the pharmacokinetics of orally administered kinetin and its tolerability. Researchers have demonstrated the effect of kinetin in improving splicing in the plasma of familial dysautonomia patients; further clinical trials are needed to determine if kinetin is able to assert this effect in the CNS.18, 19

Other effects

Kinetin has been shown to inhibit platelet aggregation in vitro and in mice. Bleeding times increased with administration of a kinetin bolus, possibly via inhibition of thromboxane A2 or free radical scavenging on the surface of activated platelets.1, 20

Dosing

Information is limited. Oral kinetin has been trialed in patients with familial dysautonomia at maximum dosages of 23.5 mg/kg/day for up to 28 days.18, 19

Topical applications are available at 0.03% to 0.1% strengths.14, 15

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. In vitro studies suggest nonmalignant cells may also be affected by the growth-suppressive effects of kinetin riboside.7

Interactions

No clinical data are available. As bleeding times increased with administration of a kinetin bolus in mice, an interaction with antithrombotic agents might be anticipated with systemic use.20

Adverse Reactions

Oral administration of kinetin has been studied in very limited trials. Patients reported nausea as kinetin dosages increased. Headache, rash, diarrhea, and tinnitus were uncommonly reported.18, 19 Information on adverse reactions due to topical application of kinetin is limited.1 Case reports of reactions to commercial topical preparations are lacking.

Toxicology

In rodents, only extremely high dosages were toxic.18 Information in humans is lacking; in limited clinical trials, modest reversible increases in liver enzymes were observed. A decreased platelet count was observed in 1 patient. No effect was observed on blood pressure, heart rate, weight, or neurological examination.18, 19

References

1. Barciszewski J, Massino F, Clark BF. Kinetin—a multiactive molecule. Int J Biol Macromol. 2007;40(3):182-192.16899291
2. Voller J, Zatloukal M, Lenobel R, et al. Anticancer activity of natural cytokinins: A structure–activity relationship study. Phytochemistry. 2010;71(11-12):1350-1359.20553699
3. Choi BH, Kim W, Wang QC, et al. Kinetin riboside preferentially induces apoptosis by modulating Bcl-2 family proteins and caspase-3 in cancer cells. Cancer Lett. 2008;261(1):37-45.18162289
4. Tiedemann RE, Mao X, Shi CX, et al. Identification of kinetin riboside as a repressor of CCND1 and CCND2 with preclinical antimyeloma activity. J Clin Invest. 2008;118(5):1750-1764.18431519
5. Cheong J, Goh D, Yong JW, Tan SN, Ong ES. Inhibitory effect of kinetin riboside in human heptamoa, HepG2. Mol Biosyst. 2009;5(1):91-98.19081935
6. Cabello CM, Bair WB 3rd, Ley S, Lamore SD, Azimian S, Wondrak GT. The experimental chemotherapeutic N6-furfuryladenosine (kinetin-riboside) induces rapid ATP depletion, genotoxic stress, and CDKN1A(p21) upregulation in human cancer cell lines. Biochem Pharmacol. 2009;77(7):1125-1138.19186174
7. Dudzik P, Dulinska-Litewka J, Wyszko E, et al. Effects of kinetin riboside on proliferation and proapoptotic activities in human normal and cancer cell lines. J Cell Biochem. 2011;112(8):2115-2124.2146553510.1002/jcb.23132
8. Karagiannis CS, Pappelis AJ. Effect of abscisic acid, gibberellic acid, indoleacetic acid, and kinetin on selective ribosomal cistron regulation in quiescent and senescent onion leaf base tissue. Mech Ageing Dev. 1994;76(2-3):145-155.7885061
9. Rattan SI, Clark BF. Kinetin delays the onset of ageing characteristics in human fibroblasts. Biochem Biophys Res Commun. 1994;201(2):665-672.8003000
10. Kowalska E. Influence of kinetin (6-furfurylo-amino-purine) on human fibroblasts in the cell culture. Folia Morphol (Warsz). 1992;51(2):109-118.1478568
11. Berge U, Kristensen P, Rattan SI. Kinetin-induced differentiation of normal human keratinocytes undergoing aging in vitro. Ann N Y Acad Sci. 2006;1067:332-336.16804007
12. Sharma SP, Kaur P, Rattan SI. Plant growth hormone kinetin delays ageing, prolongs the lifespan, and slows down development of the fruitfly Zaprionus paravittiger. Biochem Biophys Res Commun. 1995;216(3):1067-1071.7488181
13. Tournas JA, Lin FH, Burch JA, et al. 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. 2006;126(5):1185-1187.16528359
14. Wu JJ, Weinstein GD, Kricorian GJ, Kormeili T, McCullough JL. Topical kinetin 0.1% lotion for improving the signs and symptoms of rosacea. Clin Exp Dermatol. 2007;32(6):693-695.17868391
15. Chiu PC, Chan CC, Lin HM, Chiu HC. 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. 2007;6(4):243-249.18047609
16. Hims MM, Ibrahim EC, Leyne M, et al. Therapeutic potential and mechanism of kinetin as a treatment for the human splicing disease familial dysautonomia. J Mol Med (Berl). 2007;85(2):149-161.17206408
17. Lee G, Studer L. Modelling familial dysautonomia in human induced pluripotent stem cells. Philos Trans R Soc Lond B Biol Sci. 2011;366(1575):2286-2296.21727134
18. Axelrod FB, Liebes L, Gold-Von Simson G, et al. Kinetin improves IKBKAP mRNA splicing in patients with familial dysautonomia. Pediatr Res. 2011;70(5):480-483.21775922
19. Gold-von Simson G, Goldberg JD, Rolnitzky LM, et al. Kinetin in familial dysautonomia carriers: Implications for a new therapeutic strategy targeting mRNA splicing. Pediatr Res. 2009;65(3):341-346.19033881
20. Hsiao G, Shen MY, Lin KH, et al. Inhibitory activity of kinetin on free radical formation of activated platelets in vitro and on thrombus formation in vivo. Eur J Pharmacol. 2003;465(3):281-287.12681440

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

Further information

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