Are There Proven Herbal Approaches to Cancer??*

J. David Pitcher, Jr., MD

*Referencing a lecture given by Veronika Butterweck, PhD

Herbal Products

60,000,000 adults in the U.S. used herbal products in 2002

$54.00/person average cost

Approx. 3 ¼ billion $ U.S.

Perception of the public as safer, less caustic, and lower cost

Herbal Products

Used by cancer patients:Attempting to prevent cancer

Attempting to treat cancer

Attempting to treat adverse effects associated with other cancer treatments

Herbal Products

Plants useful in preventing cancer:tomatoes, garlic, green tea, soy beans

More research needed for:mistletoe

Chemotherapy induced nausea and vomiting effectively treated with:

ginger

Lycopenes

Abundant in several fruits including guava, watermelon, pink grapefruit, rosehips, and tomatoesTomato products (tomato sauce, tomato paste, ketchup) are the major dietary source of lycopeneA carotenoidA powerful antioxidant that has shown beneficial activity in several diseases (cardiovascular, cancer, Alzheimer’s disease, multiple sclerosis)

Carotenoid Biosynthesis

Lycopene undergoes cyclization of one or both end groups

alpha-carotene

beta-carotene

delta-carotene

gamma-carotene

Proven Anti-Cancer Activity??Epidemiologic and case-control studies have associated increased consumption of tomato products and greater blood concentrations of lycopene with a reduced risk of mortality from several cancers, including prostate and lung cancersIn prostate cancer a reduction in risk of 33% was found among men who consumed > 10 servings of tomato products per week (30-50mg per day) (Giovanucci, 1995, JNCI 87:1767)Levels of serum PSA were found to decline in patients who received lycopene tomato extract (Kucuk, 2001, Cancer Epidemiol Biomarkers Prev 10:86115 mg lycopene 2 x daily 3 weeks before radical prostatectomy: smaller tumors (80% vs 45%), less involvement of surgical margins (Kucuk, 2002, Exp Biol Med 227:881)

Lycopene or tomato sauce?

66 patients diagnosed by biopsy with prostate carcinoma were given either tomato sauce pasta entrees or lycopene (30 mb/day) or no tomato sauce for 3 weeks before prostatectomy

Tomato sauce consumption appeared to increase cell death in carcinomas, compared with controls (Kim, Nutrition Cancer, 2003, 47:40)

Anything else in the tomato?

Beta-carotene, gamma-carotene, epsilon-carotene, phytoene, and phytofluene are all shown to accumulate in prostate tissue upon dietary inclusion of the tomato

Acycloretinoic acid has been shown to be an oxidative product of lycopene in pig and human liver fractions

Garlic

Sulfur Compounds in Garlic

Alliin (major cysteine sulfoxide in Garlic) +Alliinase (an enzyme in fresh, whole Garlic or correctly dried Garlic powders) Allicin, the active antibiotic compoundAllicin sulfides, ajoene, dithiins, etc.

Garlic and Cancer

Ancient Egyptians, Indians, and Greeks all used garlic externally to treat tumorsDietary intake of garlic is associated with significant, dose-dependent reductions in risk of specific cancers, including colon and stomach cancer (Boon & Wong, Expert Opinion in Oncol, 2004, 5:2485)Consumption of aqueous garlic extract significantly lowered total and free PSA values; and significantly improved urinary frequency and flow (Durak, Nutrition Res, 2003, 23, 199)

Chemoprotective Properties

Induction of phase II detoxification enzymes

glutathione transferases, quinone reductase, epoxide hydrolase…

Antioxidant activity = cancer preventionFree radicals => lipid peroxidation => carcinogenesis and reduction of endogenous antioxidant levelsGarlic reduces lipid peroxidation and increases levels of vitamins C and E, superoxide dismutase, catalase, etc.

Green Tea (Camellia sinensis L.)

Flavanols, flavonols, lignans, ellagitannins

Antioxidants, anti-inflammatories

Helps prevent cancers, atherosclerosis, arthritis, Alzheimer’s disease

Flavonols in Green Tea

Antioxidant, anti-carcinogenic & anti-inflammatory flavonols contribute to Green Tea’s therapeutic effects

quercetin

myricetin

Green Tea & Cancer

A total of 20 studies reported that green tea decreases the general risk of cancer incidence, cancers of the breast, GI system, lungs, ovaries, prostate, and urinary system (Boon & Wong, Expert Opinion in Oncol, 2004, 5:2485)Amount of green tea: 1-200 g/month or 85.7 ml/day (approx 10 cups)A follow-up case control study found a significant improvement of the 5-year survival rate of bladder cancer patients who consumed green tea (Wakai, Jpn J Cancer Res, 1993, 84:1223)

Soy Products

Major compounds:genistein

daidzein

glycitein

glucosides: denistin, daidzin, glycitin

acetlyglucosides & malonylglucosides

Cancer preventive

Soy appears to have a protective effect for a variety of cancers. The evidence is not generally definitive for any specific dose or cancer typeA total of 17 case-control and cohort studies reported that intake of soy decreased the occurrence of breast, lung, stomach, endometrium, prostate, and thyroid cancer (Boon & Wong, Expert Opinion in Oncol, 2004, 5:2485)The doses reported ranged from 0.1-0.5 g/day to 140 g/dayAnti-angiogenic effects of genistein, daidzein, and biochanin A may contribute to antitumor activity

Cancer treatment

Prostate cancer: controversial resultsSoy protein supplementation (2 x daily 57 mg soy isoflavones, 3 months) lead to a trend towards longer PSA doubling time (Spentzos, Clin Can Res 2003, 9:3282No significant difference between baseline and post-treatment serum levels of total PSA (12 weeks treatment, 60 gm genistein/day)(Kumar, Prostate, 2004, 59:141)Strong antioxidants in in vitro assays

Mistletoe (Viscum album L.)

Immunostimulant

Contains lectins (Specialized proteins); ML I or viscumin, ML II & ML III that are cytotoxic to human leukemia cells

Also has viscotoxins, proteins that have some anticancer effects

Flavonoids, lignans

Mistletoe & CancerPatients with pancreatic cancer had better survival times, compared with stage-related survival reported in literature (Schafferm eyer, Complement The Med, 1998, 6:172)Several studies of cancer patients including carcinoma of the GI tract, breast, and lung cancer indicated that the mean survival time was ~ 40% longer than in the control groups (Grossarth-Maticek, Altern Ther Health Med, 2001, 7:57)In colorectal cancer patients who had undergone surgery treatment with chemotherapy + mistletoe extract had better survival rates compared with those patients receiving chemotherapy alone (Cazacu, Cancer Biother Radiopharm, 2003, 18:27)

Ginger (Zingiber officinale Roscoe)

One of ginger’s primary usage is as an antiemetic for motion sickness, postoperative nausea and vomiting, and intense morning sickness

Ginger

Gingerols make up the resinous fraction – the main pungent constituents

Anti-inflammatory

COX-2 inhibitors

Antiemetic

Antioxidant

Treatment of nausea

Encapsulated ginger given over a 2-day period (dose not provided) significantly decreased severity and duration of nause in leukemia patients (Pace, Dissertation Abstracts International, 1986, 47:3297)Powdered ginger toot, metoclopramide, ondansetron: The antiemetic efficacy of ginger was found to be equal to that of metoclopramide but ondansetron was found to be superior to both (Sontakke, Indian J Pharmocol, 2003, 35:32)Proposed mechanism: 5-HT3 antagonism

Summary & Conclusion

Overall decreased risk of cancer associated with taking garlic, green tea, soy, and tomatoesMimimum dose associated with decreased cancer risk has not been clearly definedThere is no guarantee that patients will not develop cancer if they ingest any (or all) of these herbsHerbal medicines will not replace conventional medicinesThe reviewed herbs have no significant adverse effects and do not interact negatively with conventional treatments