A new study from Asahi research shows apple polyphenol
extracts, particularly procyanidins,
inhibit skin cancer formation in mice
Slovakian scientists reported that quercetin, an
apple polyphenol extract,
protects DNA from aberrations in human
skin cancer cells.
A very promising study from 2004 shows
strong skin
cancer tumor prevention by apple polyphenol
extract in mice, and should lead to
further research. This report also details important antioxidant effects
of apple polyphenol extracts
against hydroxyl and superoxide radicals.
Further studies on apple polyphenol extracts and skin cancer
will be reported here. If you would like to be notified when more research
is published, sign up for the AP Science alerts.
J
Agric Food Chem. 2005 Jul 27;53(15):6105-11.
Procyanidin trimers to pentamers fractionated
from apple inhibit melanogenesis in b16 mouse melanoma cells.
Shoji T, Masumoto S, Moriichi N,
Kobori M, Kanda T, Shinmoto H, Tsushida T.
Fundamental Research Laboratory, Asahi Breweries, Ltd., 1-21 Midori 1-chome,
Moriya, Ibaraki 302-0106, Japan, and National Food Research Institute,
2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan.
The effects of apple polyphenols
on melanogenesis in B16 mouse melanoma cells were investigated. The
inhibitory effect of apple
polyphenols was stronger than that of arbutin or kojic acid.
Three polyphenol fractions (phenolic acid derivatives, procyanidins and
other flavonoids) were isolated, and the procyanidins were fractionated
according to the degree of polymerization using normal-phase chromatography.
The procyanidin
trimer-to-pentamer fractions were found to have the most
pronounced effect on melanogenesis. Furthermore, each procyanidin
fraction inhibited mushroom tyrosinase. No correlation between the degree of
procyanidin polymerization and tyrosinase inhibitory activity was observed.
Nevertheless, these observations suggest that
procyanidins are
effective inhibitors of tyrosinase.
PMID: 16029003 [PubMed - in process]
Mutat Res, January 3, 2005; 565(2): 105-12
Protective effect of quercetin and luteolin
in human melanoma HMB-2 cells.
K
Horvathova, I Chalupa, L Sebova, D Tothova, and A Vachalkova
Department of Experimental Therapy of Tumors, Cancer Research Institute,
Slovak Academy of Sciences, Vlárska 7, 83391 Bratislava, Slovak Republic.
Multifunctional effects of flavonoids are reported to be markedly connected
with their structure and the functional groups in the molecule. The
important role in the activity play C2-C3 double bond, hydroxyl group at C3
and the number of hydroxyl groups at phenyl ring (B). In this paper, the DNA
protective free radical scavenging potential of
quercetin (QU) and
luteolin (LU) against H(2)O(2) and their clastogenic effect alone and in
combination with melphalan (MH) were investigated in human melanoma HMB-2
cells. Elevated frequency of chromosomal aberrations induced by MH,
that at high doses have shown a variety of toxic side effects, was
statistically decreased by studied flavonoids regarding to control (QU
at the concentration of 50muM and LU already at the concentration of 20muM).
The results concerning DNA protective potential against free radicals
in HMB-2 cells demonstrated that
QU and LU have
significant effect in dose dependent manner. The percentage of QU
protective effect is 40% at the concentration 20muM, resp. 80% at the
concentration 100muM. Comparable values were obtained with LU. Results are
correlated to their structural arrangement and organization of the hydroxyl
groups.
PMID: 15661608
J. Biol. Chem., Vol. 279, Issue 11,
10670-10676, March 12, 2004
Inhibition of AP-1 and Neoplastic
Transformation by Fresh Apple Peel Extract*
Min Ding,
Yongju Lu, Linda Bowman, Chuanshu Huang, Stephen Leonard, Liying Wang, Val Vallyathan, Vince Castranova, and
Xianglin Shi
From the Pathology and
Physiology Research Branch, Health Effects Laboratory Division, National
Institute for Occupational Safety and Health, Morgantown, West Virginia
26505 and Nelson
Institute of Environmental Medicine, New York University School of Medicine,
Tuxedo, New York 10987
Consumption of fruits and
vegetables has been associated witha low incidence of cancers
and other chronic diseases. Previousstudies suggested that fresh
apples
inhibit tumor cell proliferation.Here we report that
oral
administration of apple peelextractsdecreased the number of
nonmalignant and malignant skin tumorsper mouse induced by 12-O-tetradecanolyphorbol-13-acetate
(TPA)in 7,12-dimethylbenz(a)anthracene-initiated mouse
skin. ESRanalysis indicated that
appleextract
strongly
scavenged hydroxyl(OH) and superoxide
(O2)radicals. Mechanistic studies showed that
pretreatment with apple peel extract inhibitedAP-1 transactivation induced by ultraviolet B
irradiation orTPA in JB6 cells and AP-1-luciferase reporter
transgenic mice.This inhibitory effect appears to be mediated by
the inhibitionof ERKs and JNK activity.
The results provide the
first evidencethat an extract from fresh apple peel extract may
inhibit tumorpromoter-induced carcinogenesis and associated cell
signaling,and suggest that the chemopreventive effects of fresh
applemay be through its antioxidant properties by blocking
reactiveoxygen species-mediated AP-1-MAPK activation.
Excerpts: "A previous study also indicated that whole fresh
apple may have antioxidant and
cancer chemopreventive activity.Whole-appleextracts were shown to
inhibit tumor cell proliferation and the inhibitory activity could
not be attributed solely to the ascorbate content of the apples.
Previous studies indicated that activator protein-1 (AP-1)
plays a critical role in tumor promotion. Furthermore, a recent study, using
transgenic mice, has demonstrated that
AP-1 transactivation is required for
tumor promotion. The apple
peel extract significantly inhibited UVB-induced AP-1 activation at 24 hours
and TPA-induced AP-1 activation at 72 hours post-exposure. Apple peel extract inhibited TPA-induced neoplastic transformation in a dose-dependent
manner. These data suggest that blocking of cell transformation by apple
peel extract might be through the inhibition of AP-1 transactivation.
Treatment of the mice with
appleextract decreased the tumors
per mouse at all exposure times. The maximum number of papillomas
after 20 weeks of TPA exposure in the apple-treated mice was 5.8 + 1.8 per
mouse compared with 12.8 + 3.65 papillomas per mouse in the positive control
group, indicating a greater than 50%
inhibition of papillomagenesis by oral ingestion of apple peel extract.
In addition to differences in the number of
tumors, we found that tumor size was significantly greater in the positive
control mice compared with the apple peel extract treated mice. At the end
of the experiment, there were 6 tumors greater than 4 mm in diameter in the
positive control group, whereas no
large tumors were found in the apple-treated mice.
Apple
peel extracts inhibited AP-1 activation both in vivo and in vitro,
possibly by interfering with signal transduction events involving MAP
kinases, ERKs and JNK. Cell transformation studies show that apple peel extractalso inhibited TPA-induced
cell transformation. These studies open a promising area of investigation in
understanding the molecular mechanisms responsible for the beneficial
effects of phytochemicals on health.
