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Apple Polyphenols and Colon Cancer  
  • Two studies from the U.S. have shown that apple polyphenol extracts strongly inhibit cancer cell proliferation in human colon and liver cancer cell cultures.

  • Italian researchers report that the apples may have lost much of their health benefit against colon cancer before they reach your grocery store.

  • New research findings on apple polyphenol extracts and colon cancer have been announced in the press but are not yet published in medical journals. For the latest journal publications, sign up for the free AP Science news bulletin service.

Nutrition: Antioxidant activity of fresh apples, Nature. 2000
Cold-storage affects antioxidant properties of apples in Caco-2 cells, J Nutr. 2004
Inhibition of Cancer Cell Proliferation in Vitro by Fruit and Berry Extracts and Correlations with Antioxidant Levels, J Agric Food Chem. 2004
Antiproliferative activity of apples is not due to phenolic-induced hydrogen peroxide formation, J Agric Food Chem. 2003


Nature. 2000 Jun 22;405(6789):903-4.
Nutrition: Antioxidant activity of fresh apples

Department of Food Science, 108 Stocking Hall, Cornell University, Ithaca, New York 14853-7201, USA


Abstract: Vitamin C is used as a dietary supplement because of its antioxidant activity, although a high dose (500 mg) may act as a pro-oxidant in the body. Here we show that 100 g of fresh apples has an antioxidant activity equivalent to 1,500 mg of vitamin C, and that whole-apple extracts inhibit the growth of colon- and liver- cancer cells in vitro in a dose-dependent manner.

Objective:  The antioxidant activity of 100g of fresh apple has been found to be equal to that of a 1,500-mg dose of vitamin C.  This study assesses the growth inhibiting effects of whole apple extracts on in vitro colon- and liver cancer cells, based on dose dependent comparisons.

Methods and Results: The phenolics and flavonoids contents of fresh Red Delicious apples was determined using an 80% acetone extraction process.  With and without skin the values obtained, respectively, were found to be 290.2+4.2 and 219.8+1.8 mg phenolics, and 142.7+3.7 and 97.6+3.9 mg flavonoids per 100g apple.  A total oxyradical-scavenging capacity (TOSC) assay was used to measure apple-antioxidant capacity.  This data reveals that a 1g portion of apples with skin contains a total antioxidant capacity of 83.3+8.9 TOSC.  The TOSC value unveils the antioxidant capacity of 100g of apple to be equal to that of 1,500mg of vitamin C.   Apples with skin contain a mere 5.7-mg of vitamin C, therefore leaving almost all of the antioxidant activity in apples to be due to phytochemical content.

The colon-cancer cell Caco-2 was then treated with variable amounts of apple extracts equivalent to 0, 5, 10, 20, 30, 40, and 50 mg ml^-1.  Cell proliferation was inhibited by this treatment in a dose dependent manner when extract concentrations exceeded 20 mg ml^-1, and when given optimal response time.

The proliferation of another cancer cell, HepG2 human liver tumor cell, was also inhibited when exposed to apple extract concentrations at 50 mg ml^-1.   The extract from apples containing skin had the ability to significantly reduce tumor cell proliferation in comparison to extracts from apples without skin. 

Additional information on this study from OncoLink Cancer News:

In the June 22nd issue of Nature, Dr. Rui Hai Liu and colleagues report that they used material extracted from fresh Red Delicious apples to treat a colon-cancer cell line, Caco-2. "Cell proliferation was inhibited in a dose-dependent manner after exposure to apple-extract concentrations above 20 mg/mL," they write. "At 50 mg/mL, inhibition was 43%...and 29%...for apples with [and] without skin, respectively."

The team also tested apple extract on HepG2 human liver tumor cells. They found that tumor proliferation was inhibited 57% by extract containing apple skin and 40% by extract not containing skin.


J Nutr. 2004 May;134(5):1105-9.

Cold-storage affects antioxidant properties of apples in Caco-2 cells.

Tarozzi A, Marchesi A, Cantelli-Forti G, Hrelia P.

Department of Pharmacology, University of Bologna, 40126 Bologna, Italy.

Data on the composition of phenolic antioxidant compounds present in food plants and assessment of their activity are essential for epidemiological explanation of the health benefits of fruit and vegetables. Various factors such as cultivation methods, industrial processing, and storage may affect the final concentrations of phytochemicals in food plants and their eventual bioactivity. This study investigated the influence of commercial cold-storage periods on the antioxidant properties of apples grown either by organic or integrated systems. In both cases, total phenolics and total antioxidant activity decreased only in the first 3 mo and only in apples with skin (P < 0.05), suggesting that cold storage rapidly impoverishes these properties in skin but not in pulp. Assessment of antioxidant bioactivity in vitro, measured in terms of intracellular antioxidant, cytoprotective, and antiproliferative activity in human colon carcinoma (Caco-2) cells (differentiated to normal intestinal epithelia for intracellular antioxidant and cytoprotective effects), showed strong, time-related decreases over 6 mo of cold storage for all 3 parameters (P < 0.01), irrespective of the cultivation system. These findings with integrated and organic apples further support the concept that organic systems of cultivation do not generally provide real health benefits. Moreover, the data from the present study clearly show that factors such as cold storage may affect the antioxidant properties of apples. Epidemiological studies on the cancer-preventive benefits of fruits and vegetables should take into account the cold-storage bias for apples, and possibly for other products.

PMID: 15113953 [PubMed - indexed for MEDLINE]


J Agric Food Chem. 2004 Dec 1;52(24):7264-7271.

Inhibition of Cancer Cell Proliferation in Vitro by Fruit and Berry Extracts and Correlations with Antioxidant Levels.

Olsson ME, Gustavsson KE, Andersson S, Nilsson A, Duan RD.

Department of Crop Science, Swedish University of Agricultural Sciences, P.O. Box 44, SE-230 53 Alnarp, Sweden; Department of Medicine, Lund University Hospital, SE-221 85 Lund, Sweden; and Gastroenterology Laboratory, Biomedical
Center, B11, Lund University, SE-221 84 Lund, Sweden.

The effects of 10 different extracts of fruits and berries on cell proliferation of colon cancer cells HT29 and breast cancer cells MCF-7 were investigated. The fruits and berries used were rosehips, blueberries, black currant, black chokeberries, apple, sea buckthorn, plum, lingonberries, cherries, and raspberries. The extracts decreased the proliferation of both colon cancer cells HT29 and breast cancer cells MCF-7, and the effect was concentration dependent. The inhibition effect for the highest concentration of the extracts varied 2-3-fold among the species, and it was in the ranges of 46-74% (average = 62%) for the HT29 cells and 24-68% (average = 52%) for the MCF-7 cells. There were great differences in the content of the analyzed antioxidants in the extracts. The level of the vitamin C content varied almost 100-fold, and the content of total carotenoids varied almost 150-fold among the species. Also in the composition and content of flavonols, hydroxycinnamic acids, anthocyanins, and phenolics were found great differences among the 10 species. The inhibition of cancer cell proliferation seen in these experiments correlated with levels of some carotenoids and with vitamin C levels, present at levels that can be found in human tissues. The same inhibition of cell proliferation could not be found by ascorbate standard alone. This correlation might indicate a synergistic effect of vitamin C and other substances. In MCF-7 cells, the anthocyanins may contribute to the inhibition of proliferation.

PMID: 15563205 [PubMed - as supplied by publisher]


J Agric Food Chem. 2003 Mar 12;51(6):1718-23.

Antiproliferative activity of apples is not due to phenolic-induced hydrogen peroxide formation.

Liu RH, Sun J.

Department of Food Science and Institute of Comparative and Environmental Toxicology, Cornell University, Ithaca, New York 14853-7201, USA.

Anticancer compound screening of natural products using tumor cell lines has been commonly used to identify anticancer drugs. Two highly significant anticancer drugs, paclitaxel (Taxol) and camptothecin, were discovered using tumor cell lines by the U.S. National Cancer Institute (NCI) screening program of plants. It has been recently reported that the inhibition of cancer cell proliferation by fruit extracts was indirectly caused by phenolic-induced H(2)O(2) production in the cell culture media, suggesting that many previously reported effects of flavonoids and phenolic compounds on cultured cells might be from an artifact of H(2)O(2)-induced oxidative stress. The objective of the present study was to determine if apple extracts induced H(2)O(2) formation in common cell culture media and to investigate if the antiproliferative activity of apple extracts was due to phenolic-induced H(2)O(2) formation. It is reported here that apple extracts did not induce H(2)O(2) formation in WME, DMEM, or DMEM/Ham F12 media with the cell culture conditions tested. These same extracts inhibited proliferation of HepG(2) and Caco-2 cells. Therefore, antiproliferative activity of apple extracts was not due to the phenolic-induced H(2)O(2) production in cell culture media. In addition, H(2)O(2) added to the culture medium at 100 microM did not cause inhibition of cell proliferation in either HepG(2) liver cancer cells or Caco-2 colon cancer cells in vitro.

PMID: 12617611 [PubMed - indexed for MEDLINE]

(more research)
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