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Skin Cancer  
  • 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 with a low incidence of cancers and other chronic diseases. Previous studies suggested that fresh apples inhibit tumor cell proliferation. Here we report that oral administration of apple peel extracts decreased the number of nonmalignant and malignant skin tumors per mouse induced by 12-O-tetradecanolyphorbol-13-acetate (TPA) in 7,12-dimethylbenz(a)anthracene-initiated mouse skin. ESR analysis indicated that apple extract strongly scavenged hydroxyl (OH) and superoxide (O2) radicals. Mechanistic studies showed that pretreatment with apple peel extract inhibited AP-1 transactivation induced by ultraviolet B irradiation or TPA in JB6 cells and AP-1-luciferase reporter transgenic mice. This inhibitory effect appears to be mediated by the inhibition of ERKs and JNK activity. The results provide the first evidence that an extract from fresh apple peel extract may inhibit tumor promoter-induced carcinogenesis and associated cell signaling, and suggest that the chemopreventive effects of fresh apple may be through its antioxidant properties by blocking reactive oxygen species-mediated AP-1-MAPK activation.

Full text of this study is available here in PDF format.

Excerpts: "A previous study also indicated that whole fresh apple may have antioxidant and cancer chemopreventive activity. Whole-apple extracts 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 apple extract 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 extract also 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.

(more research)

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