Phytochemical, Cancer Risk and Prevention

Meredith College FN 601

Research Summaries

Winnie Lin, MS, DTR

Phytochemical, Cancer Risk and

Prevention

Background

Cancer Statistics

Top 10 Cancer Sites. http://apps.nccd.cdc.gov/uscs/toptencancers.aspx. Accessed February 8, 2015.

http://apps.nccd.cdc.gov/uscs/toptencancers.aspx

All Races

Characteristic Overall Men Women

All Cancers 64.9% 64.9% 65%

Age group at diagnosis

0-44 years 80.5% 75.7% 83.5%

45-54 years 71.4% 65.5% 76.3%

55-64 years 68.2% 67.9% 68.6%

65-74 years 64.0% 66.8% 60.1%

75+ years 51.8% 55.0% 48.8%

Specific primary site

Lung and bronchus 18.1% 15.4% 21.2%

Colon and rectum 63.4% 62.8% 63.9%

Female breast NA NA 88.1%

Cervix uteri NA NA 67.5%

Prostate NA 97.4% NA

Cancer Survivorship and Risk Factors

Risk Factors (ACS): tobacco use, infection, diet and body composition, and radiation

Preventions: lifestyle and diet modifications, i.e. red meat and colon cancer, salts and preservatives and gastric cancer

33% of common cancers in high-income countries are preventable through adapting a healthy lifestyle

United States Cancer Statistics: 1999–2011 Incidence and Mortality Web-based Report. www.cdc.gov/uscs. Accessed February 8, 2015.

American Cancer Society http://canceratlas.cancer.org/risk-factors/cancer-risk-factors/. Accessed February 8, 2015

http://www.cdc.gov/uscs

http://canceratlas.cancer.org/risk-factors/cancer-risk-factors/








Nutrigenetics “[I]dentify the genetic markup of a particular

individual co-ordinates his or her response to various

dietary nutrients.”

5,10-methylenetetrahydrofolate reductase (MTHFR)

gene is likely to require a more bioavailable form of

folate for optimal health.

Twin studies have shown that the risk of identical

twins to develop the same cancer is <10%, of which

cancer risk is increased only if there is gene-diet

interaction .

Gaboon, NEA. Nutritional genomics and personalized diet. The Egyptian Journal of Medical Human

Genetics 2011; 12: 1-7.

Krause Food and The Nutrition Care Processes

Chemoprevention The intake of foreign agents in order to restrain induction,

to prevent or slow the progression of cancer, or reversal of carcinogenesis at a premalignant stage.

A use of pharmaceutical or nutraceutical agents, i.e. phytochemicals via inactivation of reactive oxygen species (ROS), or interruption of cell signaling pathways.

González-Vallinas et al. have suggested that “the strategies to research phytochemicals should mimic those in the development of new targeted antitumor drugs.”

Primary (avoidance), secondary (detection and elimination), and tertiary (preventing recurrence, progression, and disease-related complications)

Gaboon, NEA. Nutritional genomics and personalized diet. The Egyptian Journal of Medical Human Genetics 2011; 12: 1-7.

Krause Food and The Nutrition Care Processes

Jaganathan SK, Vellayappan MV, Narasimhan G,et al. Chemopreventive effect of apple and berry fruits against colon cancer. World J

Gastroenterol. 2014; 20(45): 17029-17036 DOI: http://dx.doi.org/10.3748/wjg.v20.i45.17029

González-Vallinas M, González-Castejón M, Rodríguez-Casado A, Ramírez de Molina A. Dietary phytochemicals in cancer prevention and

therapy: a complementary approach with promising perspectives. Nutrition Reviews. 2013; 71 (9): 585-599. DOI: 10.1111/nure.12051.

Alberts DS, Hess LM. Fundamentals of Cancer Prevention. New York, Springer Verlag; 2008.

http://dx.doi.org/10.3748/wjg.v20.i45.17029

Phytochemical

Dietary phytochemicals in cancer prevention and therapy: a complementary approach with promising

perspectives. Margarita González-Vallinas et al.



Phytochemical

Phytochemical



Jaganathan SK et al.

Chemopreventive effect of apple and

berry fruits against colon cancer

12 studies were reviewed on the effectiveness of

apple and berry juices in colon cancer prevention

7 studies of polyphenols from apple juice

hydroxycinnamic acids

flavan-3-ols/procyanidins

flavonols, dihydrochalcones, and

anthocyanins

5 studies of anthocyanin-rich extracts (AREs), β-carotene, tangeretin from berry juice.

Jaganathan SK, Vellayappan MV, Narasimhan G,et al. Chemopreventive effect of apple and berry fruits against

colon cancer. World J Gastroenterol. 2014; 20(45): 17029-17036 DOI: http://dx.doi.org/10.3748/wjg.v20.i45.17029


4 in vitro studies using colon cancer cell lines to study the

effect of apple juice on cancer cells, PKC activity in HT29

cells, oxidative damage, presence of butyl hydroperoxide-

induced ROS, cytochrome P450 1A1 enzyme and other

enzymes relevant to cancer etiology

Artificial mixture imitating the natural polyphenolic property is less

effective than its natural counterpart, so as the isolated components

than the mixtures.

In addition, SCFA has increased 1.5 fold in fermentation caused by

human fecal flora than non-fermented samples; it is known to stimulate

apoptosis.

3 in vivo studies using rat models studied the numbers of

large aberrant crypt foci and stimulation of redox-sensitive

gene expression.

Apple juices have no cancer preventative bioactivity in obese rats, while

pre-neoplastic lesions in the rats were reduced at different rates

according to the quantity of apple juices fed. Jaganathan SK, Vellayappan MV, Narasimhan G,et al. Chemopreventive effect of apple and berry fruits against colon cancer. World J

Gastroenterol. 2014; 20(45): 17029-17036 DOI: http://dx.doi.org/10.3748/wjg.v20.i45.17029


3 in vitro studies using human intestinal carcinoma cells

and the effect of AREs and flavonoids on their growth .

Those cell growths are inhibited while NCM 460, normal epithelial

cells are found to grow unaffectedly.

2 in vivo studies demonstrated purple corn extract and

lyophilized black raspberries

Decrease in the prevalence of aberrant crypt foci and early

colon cancer lesions

Inhibit colorectal cancer and/or polyp tissue.

And, low dose of mirtocyan is associated with reduced circulating

insulin-like growth factor-1, which is procarcinogenic.




Cloudy liquid is found to be more effective than clear and smoothie apple juices

2 apples per day for humans may provide 4-10 mg procyanidin to attain similar effect

22 grams of chokeberry extract to obtain 1.3 grams of cyanidin-3-glycoside (chrysanthemin), an anthocyanin derivative.

Limitations of the studies are those results are yielded in vitro or in rat models which may not be as effective as in human subjects

The quantity of each phytochemicals required is not demonstrated in every study reviewed.

More large scale human trials are required to establish the validity and practicality of fruit juice’s chemopreventive effects in human colon cancer.




Park et al.

Morin, a flavonoid from moraceae, induces

apoptosis by induction of BAD protein in

human leukemic cells

Investigated the anti-cancer activity of morin in human

leukemic cells

A flavonoid originally isolated from Moraceae family

mulberry figs and Chinese herbs

Regulates the inflammatory response, and suspenses

carcinogenesis and cancer progression.

Apoptosis is the major mechanism that is suggested to be

responsible for the anti-cancer effects of fruits and

vegetables.

Park C, Lee WS, Go S, Nagappan A et al. Morin, a Flavonoid from Moraceae, Induces Apoptosis by Induction of

BAD Protein in Human Leukemic Cells. Int. J. Mol. Sci. 2015, 16, 645-659; doi:10.3390/ijms16010645.

Park C, Lee WS, Go S, Nagappan A et al. Morin, a Flavonoid from Moraceae, Induces Apoptosis by Induction of BAD Protein in

Human Leukemic Cells. Int. J. Mol. Sci. 2015, 16, 645-659; doi:10.3390/ijms16010645.

HL-60, K562, THP-1, and U937 human leukemia cells from the American type culture collection (Manassas, VA, USA)

Morin obtained from Aging Tissue Bank (Pusan, Korea)

Cells were treated in the cell viability essay, MTT, for 48 hours to investigate the anti-cancer activity

Absorbance of each well was measured a 540 nm with an enzyme-linked immuosorbent assay (ELISA) reader (Sunnyvale, CA, USA)

Then, the cells were harvested and lysed, followed by flow cytometry analysis to measure the mitochondrial membrane potential and ROS generation.

Various analyses such like Western blot, colorimetric assay were performed.

Significant difference by ANOVA with p<0.05



U937 cells were most sensitive to morin

Morin induced caspase-dependent apoptosis through an intrinsic pathway by up-regulation of BAD proteins in U937 cells.

The maximum concentration used in the study is 2-5 folds higher than other studies investigating its antitumor effect.

Morin also performed activities leading to apoptosis in human leukemia HL-60 cells 1) promoted ROS and Ca2+ productions,

2) disruptions of mitochondria membrane potential, and

3) activated caspase-3 and caspase-9

In conclusion, morin might be useful in the treatment of human hematopoietic cancer cells.



Miller et al.

Phytochemicals and Cancer Risk: A

Review of the Epidemiological

Evidence

Conducted a systematic review, includes a total of 96 publications, to

investigate the associations between phytochemicals and cancer risk.

Inclusion criteria:

1) prospective cohort study design;

2) human population;

3) outcome of primary cancer;

4) serum or plasma marker, urinary metabolite, or dietary intake captured; and

5) phytochemicals, whether dietary intake, plasma, serum, or urine were

quantified.

Exclusion criteria:

1) case-control study design;

2) outcome of metastasis, secondary cancers, recurrence, or mortality;

3) outcome of nonmelanoma skin cancer;

4) only β-carotene or other vitamins or minerals examined;

5) only food examined, rather than specific phytochemicals;

6) animal and cell culture models; and

7) only intermediate makers used as outcome.

Miller PE, Snyder DC. Phytochemicals and cancer risk: a review of the epidemiological evidence. Nutrition in

Clinical Practice. 2012; 27 (5): 599-612. DOI: 10.1177/0884533612456043.

However, studies focusing on β-carotene alone are

also excluded due to its extensiveness in current

literatures. Thus, no randomized controlled trials

(RCTs) are included in this review.



Carotenoids:

55 studies are examined; the most commonly studied carotenes are

α-carotene, β-carotene, and lycopene for their antioxidant

properties which is considered the main mechanism for cancer

prevention.

Other mechanisms include their ability to modulate intercellular

communication via gap junctions, alter intracellular signaling

pathways, and enhance immune function.

2 studies demonstrated an inverse relationship among higher level of

β-carotene with renal cancer cells, while 1 study found a null

association .

4 studies reported an inverse relationship among β-cryptoxanthin and

lung cancer while 2 other studies fun null associations.

No significance reported for most other carotenoids and cancer site

studies.

But, longer duration of β-carotene supplementation may increase lung

cancer risk .



Phytosterols: only 1 epidemiological study examining phytosterol and no effect on cancer risk with greater intake, despite the promising results shown in animal and cell culture studies.

Isothiocyanates: 4 out of 5 studies reviewed have shown a prospective effect of higher levels of Isothiocyanates.

Chlorophyll: although animal and cell culture studies have identified the plausible mechanism of chlorophyll and reduced cancer risk, the only epidemiological study did not suggest a significant relationship among them.

Phytoestrogens: 39 studies are examined. Greater levels of total flavonoid or specific types of flavonoids are found to be inversely associated with lung, breast , stomach, prostate, pancreatic, ovarian, and/or colorectal cancers .

Most consistent association is found with lung cancer.



In summary, an isolated study for any phytochemicals is

limited due to their synergetic actions in cancer risk

reduction, whether among other phytochemicals or dietary

nutrients.

10 studies reported an increase cancer risk with higher

dietary intakes or serum, plasma, or urine metabolite levels

of certain phytochemicals.

There is insufficient evidence to recommend a single

phytochemical supplementation to reduce cancer risk.



Take Home Message Phytochemicals, such as phenols and anthocyanin (from apples and

berries) have protective features against growth of cancer cells, but

the quantity and effectiveness in humans are still uncertain.

Rossi et al. reviewed a number of phytochemicals commonly found in

beverages we drink and their chemopreventive properties. Since

there is no existing chemopreventive agent on the market, drinking

beverages rich in phytochemicals, namely EGCG in green tea, cocoa

in chocolates, caffeine in coffee, may be “an easy way to drink our

prevention.”

Majority of the studies are done in animals and cell cultures, the

effects of phytochemicals on cancer prevention or inhibition are

based on targeting the type of cells, cell signaling, cell growth, etc.

without interference of any other metabolic activities those are taking

place constantly in a human body.

Up to this date, there is insufficient evidence to recommend a

single phytochemical supplementation to reduce cancer risk. Rossi T, Gallo C, Bassani B, Canali S, Albini A, Bruno A. Drink your prevention: beverages with cancer

preventive phytochemicals. Polskie Archiwum Medycyny Wewnetrznej. 2014; 124 (12): 713-719.

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Phytochemical, Cancer Risk and Prevention

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