Plant Physiology 132:1135-1136 (2003)
© 2003 American Society of Plant Biologists
THE HOT AND THE CLASSIC
KINETIN: THE ELIXIR OF LIFE?
In a department store the other day, as I diverted my eyes from the heavily
rouged women with the free samples of cologne, I was surprised to see the word
"kinetin" enter into my field of vision. What were boxes of
kinetin lotions doing amid all these cosmetics I wondered? One of the boxes
claimed that its contents contained kinetin, "an anti-aging discovery
found in green leafy plants and recommended by dermatologists. It has been
clinically proven to deliver dramatic results without the irritating side
effects or sun sensitivity associated with retinoids and alpha-hydroxy acids.
This lotion helps reverse, delay and prevent visible signs of skin aging and
sun damage while maximizing skin's ability to retain moisture. Unlike topical
exfoliation with acids, this unique kinetin formula works deep within the
skin's surface layers to produce dramatic results without irritation."
Skeptical, I went to the original literature and found that kinetin does,
indeed, appear to be a powerful natural anti-oxidant with anti-ageing effects
(Weinstein et al., 1997 ;
Rattan, 2002). Kinetin appears
to have pluripotent effects in protecting DNA and protein from oxidative and
glyoxidative damage.
Kinetin: An Artifact?
Although kinetin (N-6-furfuryladenine) was the first cytokinin to be
isolated (Miller et al., 1955),
its source (autoclaved DNA) suggested initially that it might not be a natural
compound. More recently, kinetin has been detected in commercially available
DNA, in freshly extracted cellular DNA from human cells, and in plant cell
extracts (Barciszewski et al.,
1997). It has been suggested that kinetin is associated with plant
DNA and is synthesized as a secondary product of DNA oxidation
(Barciszewski et al., 2000b).
Most of the experimental data point toward kinetin acting as a strong
antioxidant in vitro and in vivo. Indeed, kinetin has been found to inhibit
oxidative and glycoxidative protein-damage generated in vitro
(Verbeke et al., 2000) and
protects DNA against oxidative damage mediated by the Fenton reaction
(Olsen et al., 1999).
Kinetin Delays Onset of Fibroblast Ageing
Like several other N6-substitured purine cytokinins,
N6-furfuryladenine (kinetin) retards senescence in plants
(Barciszewski et al., 2000a).
Rattan and Clark (1994)
observed that an addition of 40 to 200 µM kinetin in the culture
medium of human fibroblasts both delayed the onset and decreased the extent of
many of the ageing characteristics that appear during serial passaging of
normal cells in culture. These effects were most pronounced in cultures in
which kinetin was present continuously on the culture medium. Upon removal of
kinetin, some ageing characteristics began to reappear within a few population
doublings. Age-related changes that are affected by kinetin include
morphological alterations, growth rates, cell size, cytoskeletal organization,
macromolecular synthesis, and the intensity of autofluorescence due to the
senescence-related compound lipofuscin. Although many anti-ageing factors
promote carcinogenesis, this is not the case with kinetin in this in vitro
system: The anti-ageing effects of kinetin were achieved without any increase
in the cell culture lifespan in terms of maximum proliferative capacity in
vitro. Hipkiss (2001) has
pointed out that kinetin and three other agents that delay senescence in
cultured cells (aminoguanidine, N-t-butylhydroxylamine, and carnosine) all
react with glycoxidized proteins and possess anti-oxidant activity, suggesting
that pluripotency may be a necessary prerequisite for effective anti-ageing
activity.
Long-Lived Fruitflies
The median lifespan of the fruitfly Zaprionus paravittiger is 35
d, and even the most elderly do not live much more than 70 to 75 d. Sharma et
al. (1995) reported that low
levels of kinetin added to the diet of the fruitflies raised the median
lifespan of males to 40 d, and the median lifespan of females to 63 d. The age
of the most elderly males flies climbed from 70 to 79 d, and the most elderly
females from 76 to 91 d. Higher concentrations of kinetin were toxic. Kinetin
also slowed the developmental process: control larvae took 277 h to reach
maturity, whereas kinetin-treated larvae took 327 h. The anti-ageing effects
of kinetin, however, were not due primarily to this slowing-down of
development, but rather to a reduction in the age-specific death rates
throughout the adult lifespan. In a subsequent study, Sharma et al.
(1997) reported that the egg
laying capacity of kinetinfed fruitflies was reduced drastically as compared
with those kept on a normal diet. These results support the view that improved
maintenance of the soma and prolongation of its life is achieved at the cost
of decreased re-productive activity.
Kinetin Helps Prevent Blood Clots
Kinetin is known to have anti-oxidative properties in plants, such as
preventing the oxidation of unsaturated fatty acids in membranes
(Leshem, 1988). Since
intravascular thrombosis is believed to involve platelet adherence and
aggregation, and since the activation of platelets leads to the production of
free radicals in platelets, Hsiao et al.
(2003) examined whether kinetin
had an inhibitory activity on free radical formation in activated platelets in
vitro and on thrombus formation in vivo. Kinetin (70 and 150 µM)
reduced the electron spin resonance (ESR) signal intensity of hydroxyl
radicals in collagen-activated platelets, and was effective in reducing the
mortality of ADP-induced acute pulmonary thromboembolism in mice (Mus
musculus) when administered intravenously. Intravenous injection of
kinetin significantly prolonged the bleeding time by approximately twofold as
compared with normal saline in severed mesenteric arteries of rats (Rattus
norvegicus). A continuous infusion of kinetin (0.6 mg/kg/min) for 10 min
also significantly increased the bleeding time by about 2.3-fold, and the
bleeding time returned to baseline within 120 min after cessation of kinetin
infusion. Platelet thrombi formation was induced by irradiation of mesenteric
venules with filtered light in mice pre-treated intravenously with fluorescein
sodium. When kinetin was administered at 13 and 14 mg/kg in mice pre-treated
with fluorescein sodium (5 mg/kg), the occlusion time was significantly
prolonged. These results suggest that kinetin has effective free
radical-scavenging activity in vitro and antithrombotic activity in vivo.
Treatment with kinetin may lower the risk of thromboembolic-related disorders.
Therefore, kinetin may be a potential therapeutic agent for arterial
thrombosis, but its toxicity must be further assessed.
Kinetin and Cancer
Acute myeloid leukemia cells do not undergo the differentiation that
normally leads to functional blood cells. Instead, they are arrested at
immature stages of development. Ishii et al.
(2002) examined the effects of
various adenine analogues on the growth and differentiation of human myeloid
leukemia HL-60 cells. Kinetin, as well as isopentenyladenine and benzyladenine
were very effective in inducing morphological changes in the cells into mature
granulocytes. On the other hand, cytokinin ribosides such as kinetin riboside,
isopentenyladenosine, and benzylaminopurine riboside were the most potent for
growth inhibition and apoptosis. These results suggest that both cytokinins
and cytokinin ribosides can induce granulocytic differentiation of HL-60
cells, but cytokinin ribosides also induce apoptosis prior to the
differentiation process.
Peter V. Minorsky
Department of Natural Sciences Mercy College Dobbs Ferry, NY
10522
FOOTNOTES
www.plantphysiol.org/cgi/doi/10.1104/pp.900083.
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