Oral gel contains cancer-preventing compounds derived from black raspberries

Author: Maria Perno Goldie, RDH, MS, with the assistance of Allison Walker

Maria Perno Goldie (MPG): I had the opportunity to interview Dr. Susan Mallery, who is a humble as she is intelligent. I had the assistance of Allison Walker, a freelance journalist who has been involved in dental publishing for more than 20 years.

Dr. Susan Mallery (SM) is a Professor in the Division of Oral Surgery, Oral Pathology, and Anesthesiology at The Ohio State University, College of Dentistry, in Columbus, Ohio. Her research interests include oral cancer initiation, AIDS-related oral cancer and chemoprevention. Dr. Mallery has published articles in journals such as Cancer Research, Cancer Prevention Research, Molecular Pharmaceutics, Carcinogenesis and Clinical Cancer Research, to name a few.

She graduated from The Ohio State University with her DDS and later returned to receive her oral pathology specialty training and a PhD in Pathology. Dr. Mallery is licensed by the Ohio State Dental Board and board certified by the American Board of Oral Pathology and American Academy of Oral Pathology. She belongs to the American Academy of Oral Pathology, American Board of Oral Pathology, American Association for Cancer Research, and is a Fellow of the American Association for the Advancement of Science. She is a consultant at The Ohio State University and James Cancer hospitals.

MPG: Oral squamous cell carcinoma (OSCC) will be diagnosed in more than 36,000 Americans this year and has a particularly high mortality rate—as it will kill approximately 8,000 patients this year. As excisional surgery is the primary treatment for OSCC—even those patients who are cured suffer loss of tissues critical for esthetics, speech and eating. Due to OSCC’s high rates of morbidity and mortality and its high socio-economic impact, a strategy to prevent progression of precancerous oral lesions to OSCC is more appealing.

Currently, precancerous oral lesions are surgically removed—with either a blade or laser—and the tissues evaluated microscopically. Discouragingly, approximately 30% of lesions that are completely removed as confirmed by microscopic evaluation recur and some progress to OSCC. Dr. Mallery has dedicated her nearly 30-year career to studying new strategies to preventing oral cancer. Her research has been supported by funding from the National Cancer Institute (NCI) of the National Institutes of Health (NIH) and The Ohio State University (OSU) Center for Clinical and Translational Science. It is also funded by the Fanconi Anemia Research Fund, a grassroots organization whose mission is to find effective treatments and a cure for Fanconi anemia and to provide education and support services to affected families worldwide. Dr. Mallery stresses that she is a part of a team, and that the research is truly a team effort.

Fanconi anemia (FA) is one of the inherited anemias that leads to bone marrow failure (aplastic anemia). It is a recessive disorder: if both parents carry a defect (mutation) in the same FA gene, each of their children has a 25% chance of inheriting the defective gene from both parents. When this happens, the child will have FA. Fanconi anemia patients have an extremely high risk of developing squamous cell cancers in areas of the body in which cells normally reproduce rapidly, such as the oral cavity, esophagus, the gastrointestinal tract, the anus, and the vulva. FA patients may develop these cancers at a much earlier age than people without Fanconi anemia.

Patients who have had a successful bone marrow transplant and, thus, are cured of the blood problems associated with FA, still must have regular examinations to watch for signs of cancer. Head and neck squamous cell carcinoma (HNSCC) is a significant threat for people with FA, regardless of bone marrow transplantation status. Not only is the incidence of HNSCC considerably higher than in the general population (500-700 times higher), patients with FA present with these types of cancers at a younger age than those without FA – the median age is 27 years. Regular screenings are critically important.

MPG: Dr. Mallery, you have been investigating a number of agents to identify new therapeutics that can suppress the conversion of pre-cancerous to cancerous cells (chemoprevention), in particular, anthocyanins. Can you explain this to us?

SM: Chemoprevention is a way to prevent or delay the development of cancer by taking medicines, vitamins, or other agents. My colleagues and I are using a bimodal approach. Our first breakthrough was the creation of an oral gel containing high concentrations of anthocyanins, powerful cancer-preventing compounds found in black raspberries. Study results showed that the gel, when applied to the mouth, selectively removed atypical epithelial cells for the population through either preprogrammed cell death (apoptosis) or causing terminal differentiation (making the protective keratin covering).

MPG: Can you explain the mechanism of action of these anthocyanins?

SM: As briefly mentioned above, anthocyanins—and likely other black raspberry (BRB) compounds—are capable of modulating epithelial cell growth by affecting intracellular signaling and gene expression. Also apparent from our pilot study was that some patients derived more benefit from gel application. These inter-patient differences prompted a later study to help identify the cause.

Analyses of saliva samples collected after BRB rinses were conducted to assess local pharmacokinetics and compare the capacities of three different BRB rinse formulations to provide sustained intraoral levels of anthocyanins. Not surprisingly, these studies showed that BRB metabolism was affected by three intraoral enzymatic components, i.e. (1) oral tissues, (2) saliva, and (3) oral bacteria (“microflora”).

As all three components affected BRB bioactivation and local retention, it is likely inter-patient differences in these three areas that contribute in large part to BRB gel responsiveness. We are currently conducting the logical extension study of the pilot trial, which entails inclusion of a gel-placebo and multicenter testing. Results to date have confirmed therapeutic efficacy is limited to the BRB gel formulation and not the placebo. More complex analyses—which assess the gel’s effect at the molecular level—are ongoing.

One of the largest challenges with oral cancer chemoprevention is to develop an effective, yet nontoxic strategy. Efficacy speaks for itself—the need for nontoxic is tied to the fact that many to most of these treatments will be necessary for the life of the patient. The lifelong need is tied to the fact that persons who develop precancerous oral lesions have genetic mutations in the cells that are key for future epithelial generations, i.e., epithelial stem cells. When stem cells divide (which is not very often), they make perfect copies of themselves. Consequently, if the stem cells are mutated, their daughter cells faithfully carry forward this mutation. Our BRB gel data imply that locally applied black raspberry constituents can re-direct appropriate epithelial cell growth by removing mutated cells from the overall cell population. Consistent with a food-based approach, no systemic or local toxicities occurred.

Local delivery allows for better therapeutic concentration at the site with fewer systemic side effects. With oral cancer chemoprevention given systemically, the liver, in first-pass metabolism, makes the agent less active than the parent compound. The first-pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of lost drug during the process of absorption that is generally related to the liver and gut wall. We must have a compliant patient population with local delivery, it is vital. In some cases the decision involves having multiple biopsies or applying a gel a number of times per day. Not having frequent biopsies can be a good motivator.

MPG: Dr. Mallery, you have been investigating alternatives to the surgical removal of pre-cancerous oral lesions. Can you explain what you have found in this area?

SM: We have turned our attention to identifying alternatives to the surgical removal of pre-cancerous lesions. However, we are not “there” yet. Close clinical follow up is critical. If we suspect a malignant lesion, we must first biopsy, and if it is an active lesion, place the gel to prevent recurrence.

MPG: Dr. Mallery went on to tell a story about her passion and her work in one of the studies. She related that one third of the patients in the pilot trial were “super” responders, lesions resolved clinically and histologically, and biochemical and molecular markers returned to normal after treatment. There was an intermediate group of about one third, and the last third did not respond in either a negative or positive way. The researchers wanted to determine what caused the “super” responders to react as they did. The study was done with normal, healthy people, and it was found that there is a large difference in variability in enzyme levels to recycle the product. Best responders bioactivate the product and keep it in place for a long time. Enzyme profiles are being done.

SM: Because BRB components alone are insufficient to regress some patients’ precancerous oral lesions, we have decided to introduce a second chemopreventive, the synthetic vitamin A compound, fenretinide. Fenretinide is a “bench” chemopreventive star capable of causing either differentiation or apoptosis in transformed epithelial cells. Previous fenretinide oral cancer chemoprevention trials, which relied on systemic fenretinide delivery, were unsuccessful. Although none of these studies assessed drug levels at the target site, the pill-based delivery format could not even achieve treatment-relevant blood levels. Furthermore, large systemic doses of fenretinide resulted in toxicities including night blindness and changes in blood lipid profiles.

The objective of this study was to enhance oral mucosal permeation of fenretinide by co-incorporation of propylene glycol (PG) and menthol in fenretinide/Eudragit RL PO mucoadhesive patches. Fenretinide is an extremely hydrophobic chemopreventive compound with poor tissue permeability. Co-incorporation PG or menthol in fenretinide/Eudragit RL PO patches led to significant ex vivo fenretinide permeation enhancement. Addition of PG above 2.5 wt% in the patch resulted in significant cellular swelling in the buccal mucosal tissues. These alterations were ameliorated by combining both enhancers and reducing the PG level.

After buccal administration of patches in rabbits, in vivo permeation of fenretinide across the oral mucosa was greater relative to permeation obtained from the enhancer-free patch. In vitro and in vivo release of fenretinide from the patch was not significantly increased by co-incorporation of permeation enhancers, indicating that mass transfer across the tissue, and not the patch, largely determined the permeation rate control in vivo. As a result of its improved permeation and its lack of deleterious local effects, the mucoadhesive fenretinide patch co-incorporated with 2.5 wt% PG + 5 wt% menthol represents an important step in the further preclinical evaluation of oral site-specific chemoprevention strategies with fenretinide.

Fenretinide was studied in pill form, where there was more drug in the blood versus at the site. There were also toxicity problems. My team and I always thought that fenretinide would be a good drug if delivered in a different manner.

I worked with Peter Larsen, DDS, Chair of Division, Oral Maxillofacial Surgeon, Gary Stoner, PhD, and Kashappa Goud Desai, PhD, in both trials. Steven P. Schwendeman, PhD, is a pharmaceutical chemist, Professor and Chair Department of Pharmaceutical Sciences, College of Pharmacy, at the University of Michigan. His lab developed the fenretinide patch with Kashappa-Goud Desai, PhD. Fenretinide is lipophillic, and they needed the formulation to be stable, for the patch to stick on the site, deliver drug, and allow the drug to penetrate in an aqueous environment into keratinized tissue. It is great science! These two researchers are involved with patent application for the fenretinide patch, to be placed on active or recently excised lesions.

A combination approach with these two chemotherapeutics may someday be achieved and they may be complementary or synergistic. They have different mechanisms of action and if delivered at the same time could be antagonistic. The dosing must be staggered, with initial application, and perhaps 12 hours later, delivery of the next drug. When the patch is applied to lesions, pharmacokinetic studies show no drug in the saliva. The hypothesis is for targeted delivery and uptake of fenretinide, followed by field coverage with the raspberry rinse. A published study stated that the objective was to develop fenretinide oral mucoadhesive patch formulations and to evaluate their in vitro and in vivo release performance for future site-specific chemoprevention of oral cancer. The gel was used topically at the site of the lesion or after excision.

Our goal is to create complementary oral cancer chemoprevention strategies that would permit targeted delivery directly to visible lesions as well as address the need for field coverage throughout the mouth. My colleagues and I are optimistic that optimized delivery formulations and dosing schedules for BRB and fenretinide will help make appreciable clinical progress. We aim to prevent cancerization, which is transformation of cells into cancer, or from a normal to a cancerous state.

The concept is that being exposed to toxins and metabolic enzymes can activate toxins and cause the mutated cells to become active. There is now a multi-centered NCI trial of the raspberry product in patients, based on the pilot study. There are two manuscripts, one published and one pharmacokinetic study in rabbits ready to be published. The patch is considered a device by the FDA and they must apply as an Investigational New Device (IND). It is a very safe drug.

MPG: Dr. Mallery, what is your advice about prevention of oral cancers?

SM: I recommend not using tobacco in any form, using alcohol in moderation, visiting an oral healthcare provider at least every six months, practicing good oral hygiene, living a healthy lifestyle, having good nutrition, and providing immunization against the human papillomavirus (HPV) for sons and daughters. Precancerous lesions (oral dysplasia) tend to be on the floor of mouth, lateral border of the tongue, etc. The raspberry gel is sticky, and we are trying to get the adherent patch dosage as a “burst delivery” every 15 minutes. Patients are told not to eat or drink for 30 minutes, and the patch is designed for use multiple times throughout the day. It will be a prescription agent. Research has been conducted in Dr. Schwendeman’s lab on oral cancer patients with polyglycolic acid and polylactic acid implants (properties similar to resorbable sutures) that can deliver drug in the former cancer site. We know our patient population, they may not apply something four times a day. Polymeric implants for cancer chemotherapy may be one of the answers.

MPG: I want to thank Dr. Mallery for her time and expertise. I also wish to thank Allison Walker for her assistance with this interview.

March, 2012|Oral Cancer News|

Berry Nutrition

Author: Marie Spano, M.S., R.D., Contributing Editor

Nutritionally speaking, good things come in sweet—and tart—little packages. Research is discovering berries pack a nutritional punch due to their vitamin, fiber and antioxidant content.

Botanically speaking, berries are indehiscent fruits (they don’t need to be opened to release their seeds) that ripen through the ovary wall. However, any small, edible fruit with multiple seeds is typically considered a berry.

In addition to lending flavor and brilliant colors to a wide variety of dishes, all berries are packed with an array of antioxidants, nutrients and potential health benefits. Berries that are especially antioxidant-rich include fresh crowberries, bilberries, black currants, wild strawberries, blackberries, blueberries, goji berries, sea buckthorn, blueberries and cranberries. However, the antioxidant content of berries varies based on the geographical growing condition. And, while fresh berries are an excellent source of antioxidants, total phenol content drops during processing. In fact, processed berry jams and syrup contain approximately half the antioxidant capacity of fresh berries, and juices show the greatest loss of anthocyanins and tannins due to the removal of seeds and skin (Nutrition Journal, 2010; 9:3; Journal of Agricultural and Food Chemistry, Jan 13, 2012).

Botanical berries
Shiny, scarlet-colored cranberries are rich in vitamin C, loaded with antioxidants, including flavonoids, and score higher in their ORAC score than many other fruits (“Oxygen Radical Absorbance Capacity (ORAC) of Selected Foods—2007”, USDA ARS). Cranberries are perhaps best known for the role their juice plays in the prevention of urinary tract infections (UTI) in women, particularly those with recurrent UTIs (Cochrane Database Systems Review, 2008; 23:CD001321). However, cranberries may also inhibit the growth and proliferation of some types of cancer cells (Journal of Nutrition, 2007; 137:186S-193S), reduce low-density lipoprotein (LDL) oxidation and platelet aggregation, and improve vascular function (Nutrition Reviews, 2010; 68:168-177; Nutrition Reviews, 2007; 65:490-502). In addition, polyphenols isolated from cranberries appear to inhibit the formation of cariogenic bacteria and reduce both inflammation and the production of enzymes that contribute to the destruction of the extracellular matrix in periodontal disease, making them beneficial for oral health (Journal of the Canadian Dental Association, 2010; 76:a130).

Processing and storage affects the phytochemicals found in cranberries. Anthocyanins are present at much higher levels than flavonols in cranberries, but the reverse is true for cranberry juice, due, in part, to the instability of anthocyanins. Some flavonols are also degraded during processing but to a lesser extent than anthocyanins (Critical Reviews in Food Science and Nutrition, 2009; 49:741-781).

Also leading the nutritional way is the tiny blueberry. According to the U.S. Highbush Blueberry Council, Folsom, CA, blueberries are packed with vitamin C, dietary fiber, potassium and antioxidants, with a total of 6,552 ORAC units per 100 grams. Further, many studies have indicated blueberry supplementation can help mitigate age-related neurodegenerative diseases. In one study, for example, rats fed 18.6 grams of dried blueberry extract per kilogram of diet for eight weeks showed a reversal of age-related deficits in brain and behavioral function (The Journal of Neuroscience, 1999; 19:8,114-8,121). The phytochemicals in blueberries also may help protect against some cancers. A study that identified blueberry anthocyanins also determined their ability to inhibit the growth of colon, breast, oral and, especially, prostate cancer cell lines. The same study showed blueberries were effective in inducing cell death of colon-cancer cells (Journal of Agricultural and Food Chemistry, 2006; 54:9,329-9,339).

Other less commonly consumed berries show promising health benefits. Though relatively few health-related studies have been conducted using black, white and red currants, one study using mixed berries, including currants, found that consumption of two portions of berries daily (including black currant purée on alternating days) resulted in favorable changes in high-density lipoprotein (HDL) cholesterol, blood pressure and platelet functioning (American Journal of Clinical Nutrition, 2008; 87:323-331). Red and black currants are an excellent source of vitamin C, and black currants are also an excellent source of fiber and good source of manganese and potassium.

Wolfberries, otherwise known as goji berries, contain several antioxidants, notably zeaxanthin, one of the two antioxidants found in the retina of the eye. One double-blind, placebo-controlled study in healthy elderly subjects found that, compared to placebo, daily supplementation with goji berry (13.7 grams per day) for 90 days increased plasma zeaxanthin and antioxidant levels while protecting from hypopigmentation and soft drusen accumulation (yellow deposits under the retina) in the macula of the eye (Optometry & Vision Science, 2011; 88:257-262). Additional studies have found that goji berry juice improves antioxidant biomarkers in healthy humans (Nutrition Research, 2009; 29:19-25), subjective feelings of well-being, neurologic and psychologic performance and gastrointestinal functioning (Journal of Alternative and Complementary Medicine, 2008; 14:403-412).

More research needs to be done on the health benefits of gooseberries and muscadine grape berries, but they, too, have a great nutrition profile. Gooseberries are an excellent source of vitamins A and C, and a good source of potassium and fiber. Muscadine grape berries are an excellent source of manganese, a good source of fiber and contain reseveratrol (American Journal of Enology and Viticulture, 1996; 47:57-62).

Non-botanical berries
In addition to the nutrition attributes for botanical berries, non-botanical berries, including strawberries, chokeberries, blackberries and raspberries, are also loaded with nutrients and antioxidants.

Strawberries are an excellent source of vitamin C and also contain fiber, vitamins, potassium and phytonutrients. Animal research has shown that strawberries improve indices of memory and cognitive functioning (Current Opinion in Clinical & Metabolic Care, 2009; 12:91-94), while human intervention studies indicate that strawberries (in addition to chokeberries, cranberries and blueberries; fresh, as juice or freeze-dried) lead to significant improvements in LDL oxidation, lipid peroxidation, dyslipidemia and glucose metabolism (Nutrition Reviews, 2010;6 8:168-177).

Chokeberries (Aronia melanocarpa) contain a mix of many antioxidants, including procyanidins, anthocyanins and phenolic acids. A review of studies to date on chokeberries indicate they may be a promising functional food for diseases related to oxidative stress, but more rigorous scientific research is necessary (Phytotherapy Research, 2010; 24:1,107-1,114).

Blackberries are an excellent source of vitamin C and fiber. Studies show anthocyanin-rich fractions of blackberry extracts reduce UV-induced free radical damage to skin cells (Phytotherapy Research, 2012; 26:106-112), and freeze-dried blackberries reduce esophagus and colon cancer development in rodents (Nutrition and Cancer, 2006; 54:69-78).

Raspberries are an excellent source of vitamin C, manganese and dietary fiber, and a good source of vitamin K. However, much of the interest in raspberries stems from their anthocyanin and ellagic acid content. In vitro studies show ellagic acid is protective against cancer (Journal of Nutrition and Biochemistry, 2004; 15:672-678). And this antioxidant, as well as the overall antioxidant capacity of raspberries, is similar in fresh commercial, freshly picked and frozen raspberries (Journal of Agricultural and Food Chemistry, 2002; 50:5,197-5,201).

All berries are full of antioxidants and nutrients. And, the various colors, textures and different forms of berries, including frozen, fresh, dried and pulp, make berries a versatile, nutritious, eye-appealing and tasty addition to a variety of foods and beverages.

About the author:
Marie Spano, M.S., R.D., CSCS, is a nutrition communications expert whose work has appeared in popular press magazines, e-zines and nutrition-industry trade publications. She has been an expert guest on NBC, ABC and CBS affiliates on the East Coast.

February, 2012|Oral Cancer News|

Fighting cancer through healthy living

Author: staff

The National Cancer Institute estimates that roughly one-third of all cancer deaths may be diet related. What you eat can hurt you, but it can also help you. Many of the common foods found in grocery stores or organic markets contain cancer-fighting properties, from the antioxidants that neutralize the damage caused by free radicals to the powerful phytochemicals that scientists are just beginning to explore. There isn’t a single element in a particular food that does all the work: The best thing to do is eat a variety of foods.

The following foods have the ability to help stave off cancer and some can even help inhibit cancer cell growth or reduce tumor size.

Avocados are rich in glutathione, a powerful antioxidant that attacks free radicals in the body by blocking intestinal absorption of certain fats. They also supply even more potassium than bananas and are a strong source of beta-carotene. Scientists also believe that avocados may also be useful in treating viral hepatitis (a cause of liver cancer), as well as other sources of liver damage.

Broccoli, cabbage, and cauliflower have a chemical component called indole-3-carbinol that can combat breast cancer by converting a cancer-promoting estrogen into a more protective variety. Broccoli, especially sprouts, also have the phytochemical sulforaphane, a product of glucoraphanin – believed to aid in preventing some types of cancer, like colon and rectal cancer. Sulforaphane induces the production of certain enzymes that can deactivate free radicals and carcinogens. The enzymes have been shown to inhibit the growth of tumors in laboratory animals. However, be aware that the Agriculture Department studied 71 types of broccoli plants and found a 30-fold difference in the amounts of glucoraphanin. It appears that the more bitter the broccoli is, the more glucoraphanin it has. Broccoli sprouts have been developed under the trade name BroccoSprouts that have a consistent level of sulforaphane – as much as 20 times higher than the levels found in mature heads of broccoli.

Carrots contain a lot of beta carotene, which may help reduce a wide range of cancers including lung, mouth, throat, stomach, intestine, bladder, prostate and breast. Some research indicated beta carotene may actually cause cancer, but this has not proven that eating carrots, unless in very large quantities – 2 to 3 kilos a day, can cause cancer. In fact, a substance called falcarinol that is found in carrots has been found to reduce the risk of cancer, according to researchers at Danish Institute of Agricultural Sciences (DIAS). Kirsten Brandt, head of the research department, explained that isolated cancer cells grow more slowly when exposed to falcarinol. This substance is a polyacethylen, however, so it is important not to cook the carrots.

Chili peppers and jalapenos contain a chemical, capsaicin, which may neutralize certain cancer-causing substances (nitrosamines) and may help prevent cancers such as stomach cancer.

Cruciferous vegetables – broccoli, cauliflower, kale, Brussels sprouts, and cabbage contain two antioxidants, lutein and zeaxanthin that may help decrease prostate and other cancers.

Figs apparently have a derivative of benzaldehyde. It has been reported that investigators at the Institute of Physical and Chemical Research in Tokyo say benzaldehyde is highly effective at shrinking tumors, though I haven’t seen this report. In addition, the U.S. Department of Agriculture says figs, which contain vitamins A and C, and calcium, magnesium and potassium, may curtail appetite and improve weight-loss efforts. Fig juice is also a potent bacteria killer in test-tube studies.

Flax contains lignans, which may have an antioxidant effect and block or suppress cancerous changes. Flax is also high in omega-3 fatty acids, which are thought to protect against colon cancer and heart disease. See Budwig diet for a specialized diet using flax seed oil and cottage cheese. For studies about flax seed and flax oil, go to our Important News or Archives Page.

Garlic has immune-enhancing allium compounds (dialyl sultides) that appear to increase the activity of immune cells that fight cancer and indirectly help break down cancer causing substances. These substances also help block carcinogens from entering cells and slow tumor development. Diallyl sulfide, a component of garlic oil, has also been shown to render carcinogens in the liver inactive. Studies have linked garlic — as well as onions, leeks, and chives — to lower risk of stomach and colon cancer. Dr. Lenore Arab, professor of epidemiology and nutrition at the UNC-CH (University of North Carolina at Chapel Hill) schools of public health and medicine and colleagues analyzed a number of studies and reported their findings in the October 2000 issue of the American Journal of Clinical Nutrition. According to the report, people who consume raw or cooked garlic regularly face about half the risk of stomach cancer and two-thirds the risk of colorectal cancer as people who eat little or none. Their studies didn’t show garlic supplements had the same effect. It is believed garlic may help prevent stomach cancer because it has anti-bacterial effects against a bacterium, Helicobacter pylori, found in the stomach and known to promote cancer there.

Grapefruits, like oranges and other citrus fruits, contain monoterpenes, believed to help prevent cancer by sweeping carcinogens out of the body. Some studies show that grapefruit may inhibit the proliferation of breast-cancer cells in vitro. They also contains vitamin C, beta-carotene, and folic acid.

Grapes, red contain bioflavonoids, powerful antioxidants that work as cancer preventives. Grapes are also a rich source of resveratrol, which inhibits the enzymes that can stimulate cancer-cell growth and suppress immune response. They also contain ellagic acid, a compound that blocks enzymes that are necessary for cancer cells – this appears to help slow the growth of tumors.

Studies show that consumption of green and yellow leafy vegetables has been associated with lower levels of stomach cancer.

Kale has indoles, nitrogen compounds which may help stop the conversion of certain lesions to cancerous cells in estrogen-sensitive tissues. In addition, isothiocyanates, phytochemicals found in kale, are thought to suppress tumor growth and block cancer-causing substances from reaching their targets.

Licorice root has a chemical, glycyrrhizin, that blocks a component of testosterone and therefore may help prevent the growth of prostate cancer. However, excessive amounts can lead to elevated blood pressure.

Mushrooms – There are a number of mushrooms that appear to help the body fight cancer and build the immune system – Shiitake, maitake, reishi, Agaricus blazei Murill, and Coriolus Versicolor. These mushrooms contain polysaccharides, especially Lentinan, powerful compounds that help in building immunity. They are a source of Beta Glucan. They also have a protein called lectin, which attacks cancerous cells and prevents them from multiplying. They also contain Thioproline. These mushrooms can stimulate the production of interferon in the body.

Extracts from mushrooms have been successfully tested in recent years in Japan as an adjunct to chemotherapy. PSK is made from the Coriolus Versicolor. Maitake mushroom extract is PCM4.

Nuts contain the antioxidants quercetin and campferol that may suppress the growth of cancers. Brazil nut contains 80 micrograms of selenium, which is important for those with prostate cancer. (Note: Many people are allergic to the proteins in nuts, so if you have any symptoms such as itchy mouth, tight throat, wheezing, etc. after eating nuts, stop. Consider taking a selenium supplement instead or work with someone on how to eliminate this allergy.)

Oranges and lemons contain Iimonene which stimulates cancer-killing immune cells (lymphocytes, e.g.) that may also break down cancer-causing substances.

Papayas have vitamin C that works as an antioxidant and may also reduce absorption of cancer-causing nitrosamines from the soil or processed foods. Papaya contains folacin (also known as folic acid), which has been shown to minimize cervical dysplasia and certain cancers.

Raspberries contain many vitamins, minerals, plant compounds and antioxidants known as anthocyanins that may protect against cancer. According to a recent research study reported by Cancer Research 2001;61:6112-6119, rats fed diets of 5% to 10% black raspberries saw the number of esophageal tumors decrease by 43% to 62%. A diet containing 5% black raspberries was more effective than a diet containing 10% black raspberries. Research reported in the journal Nutrition and Cancer in May 2002 shows black raspberries may also thwart colon cancer. Black raspberries are rich in antioxidants, thought to have even more cancer-preventing properties than blueberries and strawberries.

Red wine, even without alcohol, has polyphenols that may protect against various types of cancer. Polyphenols are potent antioxidants, compounds that help neutralize disease-causing free radicals. Also, researchers at the University of North Carolina’s medical school in Chapel Hill found the compound resveratrol, which is found in grape skins. It appears that resveratrol inhibits cell proliferation and can help prevent cancer. However, the findings didn’t extend to heavy imbibers, so it should be used in moderation. In addition, alcohol can be toxic to the liver and to the nervous system, and many wines have sulfites, which may be harmful to your health. Note: some research indicates that alcohol is considered a class “A” carcinogen which can actually cause cancer – see You should probably switch to non-alcoholic wines.

Rosemary may help increase the activity of detoxification enzymes. An extract of rosemary, termed carnosol, has inhibited the development of both breast and skin tumors in animals. We haven’t found any studies done on humans. Rosemary can be used as a seasoning. It can also be consumed as a tea: Use 1 tsp. dried leaves per cup of hot water; steep for 15 minutes.

Seaweed and other sea vegetables contain beta-carotene, protein, vitamin B12, fiber, and chlorophyll, as well as chlorophylones – important fatty acids that may help in the fight against breast cancer. Many sea vegetables also have high concentrations of the minerals potassium, calcium, magnesium, iron, and iodine.

Soy products like tofu contain several types of phytoestrogens — weak, nonsteroidal estrogens that could help prevent both breast and prostate cancer by blocking and suppressing cancerous changes. There are a number of isoflavones in soy products, but research has shown that genistein is the most potent inhibitor of the growth and spread of cancerous cells. It appears to lower breast-cancer risk by inhibiting the growth of epithelial cells and new blood vessels that tumors require to flourish and is being scrutinized as a potential anti-cancer drug. However, there are some precautions to consider when adding soy to your diet. Eating up to 4 or 5 ounces of tofu or other soy a day is probably ok, but research is being done to see if loading up on soy could cause hormone imbalances that stimulate cancer growth. As a precaution, women who have breast cancer or are at high risk should talk to their doctors before taking pure isoflavone powder and pills, extracted from soy.

Sweet potatoes contain many anticancer properties, including beta-carotene, which may protect DNA in the cell nucleus from cancer-causing chemicals outside the nuclear membrane.

Teas: Green Tea and Black tea contain certain antioxidants known as polyphenols (catechins) which appear to prevent cancer cells from dividing. Green tea is best, followed by our more common black tea (herbal teas do not show this benefit). According to a report in the July 2001 issue of the Journal of Cellular Biochemistry, these polyphenols that are abundant in green tea, red wine and olive oil, may protect against various types of cancer. Dry green tea leaves, which are about 40% polyphenols by weight, may also reduce the risk of cancer of the stomach, lung, colon, rectum, liver and pancreas, study findings have suggested.
Tapioca is derived from the cassava plant. It is one of the many plants that manufactures cyanide by producing a chemical called linamarine which releases hydrogen cyanide when it is broken down by the linamarase enzyme. Spanish researches have been studying the cassava and attempting to clone the genes from the plant which are responsible for producing the hydrogen cyanide and then transfer it to a retrovirus. However, funding for the project has run out. for more information on this. For a list of other foods that contain B17, go to our laetrile page.

Tomatoes contain lycopene, an antioxidant that attacks roaming oxygen molecules, known as free radicals, that are suspected of triggering cancer. It appears that the hotter the weather, the more lycopene tomatoes produce. They also have vitamin C, an antioxidant which can prevent cellular damage that leads to cancer. Watermelons, carrots, and red peppers also contain these substances, but in lesser quantities. It is concentrated by cooking tomatoes. Scientists in Israel have shown that lycopene can kill mouth cancer cells. An increased intake of lycopene has already been linked to a reduced risk of breast, prostate, pancreas and colorectal cancer. (Note: Recent studies indicate that for proper absorption, the body also needs some oil along with lycopene.)

Tumeric (curcuma longa), a member of the ginger family, is believed to have medicinal properties because it inhibits production of the inflammation-related enzyme cyclo-oxygenase 2 (COX-2), levels of which are abnormally high in certain inflammatory diseases and cancers, especially bowel and colon cancer. In fact, a pharmaceutical company Phytopharm in the UK hopes to introduce a natural product, P54, that contains certain volatile oils, which greatly increase the potency of the turmeric spice.

Turnips are said to contain glucose molaes which is a cancer fighting compound. I haven’t confirmed this.

Consumption of fruits and vegetables has been associated with decreased risk of cancers of the colon and rectum.

There are many good books on this topic, including Vern Verona’s book on “Cancer Fighting Foods.”

Blueberries: cancer-fighting flowers in disguise

Author: Julie LeBlanc


I can’t say I’ve been one for gardening. Or just liking plants, in general, for that matter. I’m the person that killed two rose bushes within two weeks while living in the school dormitories last year.

It’s things like this that make you contemplate becoming a super-villain.

Even I was amazed to find out that blueberries are not, in fact, berries at all. They’re not even fruit. claims they are “epigynous fruits” which, aside from having a name that could tongue-tie Mr. Ed, means that they are actually flowers. Tiny, blue, delicious flowers that go fabulously with vanilla ice cream.

Instead of parts like the stamen and petals falling off when the bud is ready to ripen, these organs stay attached and actually form alongside the plant ovary to create these little “false fruits.” Other veggies in this genre of plants include cucumbers, melons, bananas and figs.

Sneaky little buggers.

“The health properties of blueberries” or “Why you need another reason to eat these for dessert”:

Containing only about 40 calories in ½ a cup, blueberries have ascended to the superfood pantheon which includes, among other things, açai berries, red wine and plums. Like their cancer-fighting counterparts, blueberries contain high levels of anthocyanins and antioxidants, two phytonutrients which amp up the body’s immune system and to detoxify harmful chemicals. Some species even contain reservatrol, another phytonutrient that aids in fighting cancer and Alzheimer’s.  Red grapes and red wines are well-known for containing high amounts of reservatrol.

The growing season for blueberries typically peaks between May and June. If you’ve got a farm in your area, look into picking some on your own. You’ll never buy berries from the supermarket again. Bring your significant other, or kid sister, or your Grandma Maybelline. It’s more fun to pick berries together and you can pass the time gorging on the occasional tempting berry or pelting each other with the green, unripe ones.

Not that I condone of that sort of thing, mind you.

What this means for you: claims that the average adult should take in roughly two cups of fresh fruits a day. If possible, said fruits should range the colour spectrum. Darker fruits in reds and blues contain more antioxidants and, thus, your diet should include them as often as possible. Yes; believe it or not, the universe has colour-coded your diet. Does it get any easier? Not really. Does it get more delicious? You bet your cookie dough it does.

Chemopreventive agents in black raspberries identified

Author: staff

A study published in Cancer Prevention Research, a journal of the American Association for Cancer Research, identifies components of black raspberries with chemopreventive potential.

Researchers at the Ohio State Comprehensive Cancer Center found that anthocyanins, a class of flavonoids in black raspberries, inhibited growth and stimulated apoptosis in the esophagus of rats treated with an esophageal carcinogen.

“Our data provide strong evidence that anthocyanins are important for cancer prevention,” said the study’s lead author, Gary D. Stoner, Ph.D., a professor in the department of internal medicine at Ohio State University.

Stoner and his team of researchers fed rats an anthocyanin-rich extract of black raspberries and found that the extract was nearly as effective in preventing esophageal cancer in rats as whole black raspberries containing the same concentration of anthocyanins. This study demonstrates the importance of anthocyanins as preventive agents in black raspberries and validated similar in vitro findings. It is among the first to look at the correlation between anthocyanins and cancer prevention in vivo.

Stoner and his colleagues have conducted clinical trials using whole berry powder, which has yielded some promising results, but required patients to take up to 60 grams of powder a day. “Now that we know the anthocyanins in berries are almost as active as whole berries themselves, we hope to be able to prevent cancer in humans using a standardized mixture of anthocyanins,” said Stoner.

“The goal is to potentially replace whole berry powder with its active components and then figure out better ways to deliver these components to tissues, to increase their uptake and effectiveness. Ultimately, we hope to test the anthocyanins for effectiveness in multiple organ sites in humans,” said Stoner.

January, 2009|Oral Cancer News|