The Treatment of Colorectal Cancer using Chemotherapy and Chinese Herbal Medicine

by Tai Lahans

Introduction

In 2007, 180,000 new cases of colorectal cancer (CRC) were diagnosed in the United States (1). As a cause of cancer, CRC ranks second only to lung cancer. Approximately 60,000 deaths per year are attributed to CRC with a 5-year survival rate of about 50% (2).

Environmental, nutritional, genetic and familial factors have been found to be associated with colorectal cancers. Diets high in saturated fat, especially animal fat and low in fibre and calcium, along with a lack of exercise all contribute to CRC (3). Dietary fats increase the endogenous production, bacterial degradation and excretion of bile acids and neutral steroids, which are carcinogens, thereby promoting large bowel carcinogenesis. Excess lipids in the colon lead to an increase in the concentration of secondary bile acids which stimulate protein kinase C (PKC), a major cellular communication pathway, resulting in the promotion of cancer (4).

Modern Chinese medicine has been treating cancers, including CRC, through an integrated approach for the last sixty years (5,6). The colon and rectum are at the distal end of the gastrointestinal tube and are part of the ‘fu’ aspect of the zang fu. This hollow tube is outside the body and acts as a conduit for the transfer of exogenous nutrition. Therefore, it is constantly exposed to whatever is passing through, clean and unclean. The lower intestine is also a symptomatic aspect of the functional orb of the spleen. This orb of activity anatomically includes the stomach – the formation of chyme, pancreas – sugar and other aspects of metabolism, gallbladder – fat metabolism, small intestine – absorption of nutrients and water and to a lesser extent the large intestine – final absorption of water (7,8). The spleen, therefore, has to do with the metabolism of proteins, carbohydrates, fats and water.

The GI tube accepts outside elements for breakdown and absorption into the body interior. Like the lung, the exterior and interior relationship requires a type of tissue that offers a means for this exchange to take place. Perhaps this is why the lung and large intestine are a pair of coupled organs; their tissue types are very much the same. There must also be a mechanism for protection against outside pathogens. The Ying and its relationship to the spleen and the san jiao provides this protection through the immunoglobulins of the mucosal lining of the GI tract (9,10).

The colon is exposed to pathogenic factors, some endogenous – like bile acids, and some exogenous – like nitrates and nitrites and other food contaminants. These exposures can be broken down into two categories – damp heat and wind. Damp heat (11) can be the result of a diet high in animal fats, refined carbohydrates and some contaminants that come through the food chain. Saturated animal fats and refined foods with a high glycemic index are a form of dampness that when eaten in excess over a lifetime can result in damp accumulations like atherosclerotic plaques, polyps, obesity, pathologic mucus. These cumulative disorders are damp by nature. When they cause obstructive diseases, they create constraint and heat and can combine with heat to form damp heat.

Wind is another pathogenic influence that usually attacks the lung and causes certain kinds of upper respiratory infection. Wind and wind heat can enter the colon via external pathogens like amoebas, protozoa, bacteria, nitrates, nitrites, PCBs, Dioxin, lead, pesticides and many other chemicals. Wind heat can also develop from endogenous sources like anaerobic bacteria that evolve because of internal digestive and internal imbalances. Both Wind and Damp Heat can result in Toxin. Malignancy implies Toxin in one form or another, and it usually takes many years of constant injury from Toxin to generate malignancy (12,13). When patients with cancer are treated in an integrative approach with Chinese and conventional medicine several factors are taken into account (14):

1. The constitutional environment of the patient includes the entire terrain and associated history that built that terrain. Underlying conditions and lifestyle factors often play a role in the evolution of a cancer. The constitutional environment must be addressed to treat the cancer that is considered an end event in a long history of continuous injury. Treatment of the constitution at the beginning allows for an initiation in preventing recurrence by changing the body’s ecology, so to speak.

2. The pattern diagnosis for the cancer itself is descriptive of the way in which the cancer currently behaves. This pattern diagnosis can include the Chinese medicine diagnosis plus the stage, type and characteristics of the cancer in conventional terms. The pattern diagnosis must also be treated because it treats the environment of the cancer and may not be only cytotoxic, as is the conventional approach. Cancer is not only a local event. The pattern takes into account the immediate ecology of the terrain that allowed the cancer to happen in the first place. The constitutional and pattern diagnoses are interlinked, but the constitutional diagnosis is the inherited and the acquired ecology of the particular human body. The pattern diagnosis is how the cancer occurred within that particular constitution.

3. The treatment interventions from a conventional medical point of view are generally cytotoxic in approach and therefore, carry predictable side effects based on the intervention. The treatment interventions, especially radiotherapy, chemotherapy, hormonal and biological therapies, also have mechanisms of action by which they eliminate cancer cells. Understanding the mechanism of action and the side effects of the conventional treatment allows for an herbal intervention that potentiates the cytotoxic therapy and treats its side effectst. Potentiation means to improve outcomes for a given patient. This can take the form of improving the symptom picture, maintaining normal blood chemistries and allowing the patient to maintain the schedule of treatment, an important aspect of cytotoxic therapies. It can mean utilizing specific herbs that have been found to interfere with cancer types’ ability to turn over and multiply. It can mean the improvement of certain aspects of immune function, especially natural killer cell activity, to allow the body’s own immune system to eliminate cancer cells more effectively. Much of modern research into integrated care looks at how specific substances and combinations of those substances work against a cancer while limiting the amount of damage to healthy function.

Treatment Principles (15)

There are several treatment principles within Chinese medicine that are used in various combinations to interact with conventional therapies in cancer treatment:

1. Fu Zheng Qu Xie refers to the promotion of the overall body health including the immune system to allow the body to heal itself from within. Since deficiency can be a predisposing factor for cancer, and the cancer itself causes deficiencies, and treatment of the cancer also causes deficiencies, the use of fu zheng principles has been one of the most commonly used treatment interventions in cancer. The herbs in this category increase the rate phagocytosis and lymphocyte transformation. Some of these herbs promote the formation of antibodies and prolong the time the antibody survives. Many show marked preventive action against leukopenia, a common deficiency that interruptssilly the timing of chemotherapeutic agents, because of the risk of infection. These herbs can improve camp content in cells thus improving cellular energy. The high polysaccharide levels of many qi tonic herbs make them prime candidates for fu zheng therapy. Examples include Huang Qi (Radix Astragali), Ren Shen (Radix Ginseng) and many mushrooms like Ling Zhi (Ganoderma) and the Zhu Ling (Polyporus) (16).

2. Huo Xue Qu Yu refers to the activation of blood circulation. Stasis is often a precursor condition for cancer and is always a part of the end result. Masses and solid tumours are forms of congealed blood and/or phlegm knotted with toxin. Blood stasis syndrome is found in about 80% of cancer patients. The capillaries are twisted and knotted, preventing blood cells from moving through. High levels of platelet aggregation, high blood viscosity, high fibrinogen content and disseminated intravascular coagulopathy (DIC) are all characteristics of ‘sticky’ blood and blood stasis syndromes. This syndrome prevents the free movement of qi and blood, causes inflammation and becomes a mechanism for the deepening of latent pathogenic factors.

Herbs and formulas that regulate and activate the blood help to maintain normal blood circulation, positively affect erythrocyte and platelet aggregation and help restore microcirculation. They also help improve circulation to tumour masses thereby improving access of cytotoxic agents. They also discourage metastatic spread by disallowing cancer cells to stick in distant places and sometimes by being anti-cancer themselves (17).

3. Qing Re Jie Du is a term used to describe the removal of heat toxins with heat clearing herbs. Heat clearing and toxin removing herbs may actually slow or prevent the mutation of the DNA by heat toxins. These toxins can be chemicals, viruses, pathogens, or the result of pathological internal balances. Some heat clearing herbs are antibiotic in effect. They clear heat, inflammation, some accumulations and various toxins, including those that result in local or systemic fevers, inflammations, suppurations and abscesses. The herbs in this category contribute significantly to the antineoplastic effect of chemotherapy and radiation therapy. Shan Dou Gen (Radix Sophorae tokinensis), Bai Hua She She Cao (Herba Hedyotis diffusae), Ban Zhi Lian (Herba Scutellariae barbatae), Pu Gong Ying (Herba Taraxaci), Xia Ku Cao (Prunellae Spica) are all examples of herbs from this category (18).

4. Ruan Jian San Jie refers to the softening and dissolving of masses. Many hard tumours are tight combinations of blood and phlegm stasis. Some have a tough fibrin coating around them that makes access to the centre mass difficult. The saltiness of the sea herbs of this category increases the dynamic flow of fluids into the tumour core. Many of these herbs also improve immunity and some are antineoplastic (19).

5. Yi Du Gong Du means using poison to treat poison. Cytotoxic therapies in this category and are restricted to conventional treatments. Herbs that are poisonous are not legal for importation or use in most western countries. All of the above treatment principles are combined in various ways to address a cancer in the context of the conventional treatment with integrated Chinese medicine. The goal in this context is to regulate qi and harmonize blood, transform phlegm and drain dampness, soften the hard and dissolve nodules, dissolve toxins and stop pain, tonify the qi and nourish the blood, benefit the spleen and pacify the stomach and replenish and tonify the liver and kidneys. A formula is written based on the following criteria. Not all will be used in any given formula depending upon what is needed at that time in a patient’s treatment plan.

Tumour load reduction through attacking, dissolving, moving, detoxifying, clearing pathogenic factors, warming and cooling.
Prevention of the formation and development of further cancer or cancerous spread by harmonizing, strengthening Ying and Wei qi and clearing pathogenic factors.
Enhancement of immune function, including cellular and humoral immunity, by tonifying qi and nourishing blood, tonifying yang and generating yin, harmonizing and promoting fluids.
Maintenance of the regulating function of the endocrine system by regulating qi and blood.
Enhancement and protection of the structure and function of the viscera by tonifying the yin and yang of the zang organs solid implies organs/viscera.
Strengthening of the digestion and absorption by benefiting and tonifying the spleen.
Protection of the bone marrow and hematopoietic function by nourishing the essence.
Increasing the efficacy of conventional treatments by harmonizing the flow of qi and blood. 9. Prevention, amelioration and control of adverse side effects and diseases caused by conventional therapy.

Case study

Following is a case of a patient treated with combined conventional and Chinese medicine. Male 53 years old.

Presentation

Abdominal pain, frequent stool movements, diarrhoea, five to six times per day with blood and pus. The blood is bright red without clots.

History

Stomach ulcer occurred 10 years ago and was resolved with pharmaceutical treatment. Hypertension is controlled with antihypertensives. Normal childhood illnesses. Intestinal polyps are current and the patient has a history of polyps. Acid eructation and heart burn have been present for several years and are currently present. Chronic constipation with dry stool until one year ago. Dizziness and thirst are common. Diet is cause for concern with high fat and greasy foods, no vegetables at all, lots of dairy and ice cream and large amounts of meat. Patient does not exercise and is 40 pounds overweight. Work life is very stressful and sedentary.

Investigations

Stool sampling for parasites – negative
Barium imaging – positive for 3cm mass in transverse colon and 3 pericolic nodes that are swollen
Abdominal and pelvic CT – localized mass without metastatic spread has invaded the muscle layer and three local lymph nodes
Chest CT – negative for metastases
Liver and kidney function tests – normal
CEA – 13
CA 19-9 – 25
CBC – anaemia; RBC – 3.5; HCT – 34
Tongue – slight red, swollen, yellow greasy coat with no coating on posterior region
Sublingual vein distension – +3 (out of 4)
Pulse – wiry, forceful, slippery, spleen position weakest
Hara – cool over Spleen reflex, hot over kidney reflex, lung area very sticky and clammy, blood stasis reflex at the middle and deep positions is very tight and tender.

Histopathology

Adenocarcinoma – poorly differentiated Grade 3 (aggressive)

Symptoms

Abdominal pain especially before and with stool movement
Diarrhoea with bright red blood
Thirst for cold drinks
Dry mouth
Dizziness that is constant
Low-grade queasy feeling
Lower and middle abdominal distension after eating
Poor appetite
Sleep is poor due to worry and is hot at night but does not sweat

Diagnosis

Conventional medicine – Duke’s Stage C adenocarcinoma; T2N1M0
Chinese medicine – damp heat with liver and kidney yin deficiencies and an underlying spleen deficiency.

The patient has a long history of upper and middle digestive complaints. His lifestyle has contributed to an internal environment of yin deficiency and spleen injury. He is chronically under-hydrated and is malnourished in a way that contributes to fluid imbalances, calcium deficiency and irregular bowel movement. Chronic imbalances of this sort can result in hypertension. When combined with spleen deficiency it can lead to phlegm damp accumulation in the form of atherosclerotic plaque build-up in the arteries, polyps and abnormal mucus in the lower digestive tract, heart disease, type II diabetes, prostate cancer and other chronic conditions.

The damp heat is an excess condition caused by poor dietary choices and a deficient Spleen. The spleen deficiency, damp heat and diet are part of a self-perpetrating vicious cycle that worsens the imbalance. Yin deficiency and spleen deficiency are magnets for latent pathogenic factors. If we think of animal fats and chemicals and other insults as latent pathogens, then over a lifetime these insults can lead to an accumulation that reaches critical mass around middle age.

Treatment Plan:

1. Surgery – The surgical plan included an en bloc procedure removing one foot of colon including all of the transverse section plus removal of fifteen abdominal lymph nodes. An anastomosis was done reconnecting the remaining colon so that no colostomy was required. It is typical to remove at least one foot of colon even in smaller tumours. Better survival has been shown with wider resections.

The formula used was Chang Ai Kang Fu Tang (Colo-rectal Cancer Anti-relapse Decoction), dosage 8 grams three times daily (see note 1). It is used to prevent further spread as a result of the surgical procedure, reduce blood loss, stop swelling and pain from trauma and begin to treat the cancer prior to chemotherapy. This formula was used pre- and post-surgery. Three modifications were applied to this formula: a mild laxative was added to aide in re-establishing bowel function interrupted by anesthesia and by the surgical trauma; Yan Hu Suo (Rhizoma Corydalis),was added to ameliorate pain and Bai Jiang Cao (Herba Patriniae) was added to detoxify and begin to treat the cancer before chemotherapy was initiated.

Chang Ai Kang Fu Tang is a modern formula that increases CD3, CD4, and CD8 values. It also increases NK cells and activity. It benefits the spleen and increases the zheng qi. Huang Qi (Radix Astragali) in the formula is added in fairly high doses to aide in wound healing. The formula also gently regulates the blood to prevent clots and adhesions, a common complication of abdominal surgeries.

Chemotherapy Plan

The chemotherapy regimen began three weeks post-surgery and included Gemcitabine with 5-FU (fluouracil) and Leucovorin. Gemcitabine was added as a newer intervention at that time in a grade 3 tumour to prevent metastatic spread and recurrence. The primary side effects of Gemcitabine are neutropenia, thrombocytopenia, nausea, stomatitis, and liver and renal toxicity. Those of 5-FU are leucopenia, thrombocytopenia, nausea, stomatitis, diarrhoea, liver and renal toxicity, cardiotoxicity, lethargy and weakness. This regimen was given every three weeks.

The treatment principles used in this case:

Maintain normal blood levels, especially WBC, RBC and platelet counts.
Protect heart, liver and kidney organs.
Maintain normal digestive function, especially ameliorate nausea and diarrhoea.
Treat antineoplastically by potentiating Gemcitabine and 5-FU and by utilizing specific antineoplastic herbs (the leucovorin is a potentiating antihelminthic)
Treat the constitutional diagnosis of liver and kidney yin deficiency and the pattern diagnosis of damp heat toxin.

The formula used is Huai Hua Di Yu Tang He Bai Tou Weng Jia Jian (see note 2). The first part of the formula is a modern modification of a formula from the Pu Ji Ben Shi Fang (Classified Formulas of Universal Benefit From My Practice, by Xu Shu Wei published in 1150 ACE). Bai Tou Weng Tang (Pulsatilla Decoction) is taken from the Shang Han Za Bing Lun. These two formulas are emblematic of how ancient Chinese medicine has continued to be useful in modern times and is still used to treat illnesses in the modern context.

The combined explanation for the total formula is that it cools the intestines and stops bleeding both caused by wind heat and damp heat. It clears inflammation of the intestines, transforms and resolves toxins, treats mucus in the stool and stops diarrhoea, both of which are forms of dampness. It resolves the damp heat pattern present. It tonifies the spleen function that has been injured by a lifetime of improper eating habits. There are several antineoplastics added to relieve toxicity. Some of these antineoplastics have the combined effect of protecting the heart, liver and kidney from the toxicity of the chemotherapeutic regimen. For example, Bai Hua She She Cao (Herba Hedyotis diffusae) is an herb in the clear heat and toxin category that has been shown through pharmaceutical studies to protect heart muscle from damage by some forms of chemotherapy, like 5-FU and Adriamycin.

Conclusion

This patient went through six rounds of Gemcitabine with 5-FU and Leucovorin. He maintained normal blood values and chemistries and showed no signs of organ damage. He never received colony stimulating factors to maintain his blood values. He was given anti-emetics for two rounds and then decided to discontinue the anti-emetics because of severe constipation. He was treated for the last six rounds only with Chinese herbal medicine without nausea and other side effects. He had normal stool, normal sleep patterns, good digestion, a good appetite and good energy. His CEA and CA19-9 were monitored and continually went down indicating no interference in the chemotherapy regimen and its mechanism by the herbal medicine. At the end of treatment his CEA was 1.3 and his CA19-9 was 3.

Six years later this patient has remained well with normal scans and normal cancer markers. He reports that he feels better now than ever in his life. For two years after the conventional treatment ended he continued with herbal medicine to prevent recurrence of his aggressive and later stage CRC. He remains well.

End Notes

Note 1: Chang Ai Kang Fu Tang: Zhi Huang Qi (Radix Astragali) 20g, Chao Bai Zhu (Rhizoma Atractylodis macrocepalae) 10g, Tai Zi Shen (Radix Pseudostellariae) 15g, Zhu Ling (Polyporus) 10g, Dang Gui (Radix Angelicae sinensis) 8g, E Zhu (Rhizoma Curcumae) 8g, Ba Yue Zha (Fructus Akebiae) 20g, Bu Gu Zhi (Fructus Psoraleae) 10g, Ban Zhi Lian (Herba Scutellariae barbatae) 30g, Ban Bian Lian (Herba Lobeliae chinensis) 30g, Qing Hao (Herba Artemisiae annuae) 10g and Chai Hu (Radix Bupleuri) 10g.
Note 2: Huai Hua Di Yu Tang He Bai Tou Weng Jia Jian: Huai Hua Mi (Sophorae Flos immaturus) 10g, Di Yu (Radix Sanguiaorbae) 10g, Bai Jiang Cao (Herba Patriniae) 30g, Ku Shen (Radix Sophorae flavescentis) 10g, Ma Chi Xian (Herba Portulacae) 30g, Huang Bai (Cortex Phellodendri) 10g, Bai Tou Weng (Herba Potentillae chinensis) 15g, Yi Yi Ren (Semen Coicis) 30g, Chi Shao (Radix Paeoniae rubra) 15g, Xian He Cao 20g, Cang Zhu (Rhizoma Atractylodis) 10g, Bai Zhu (Rhizoma Atractylodis macrocephalae) 10g, Hou Po (Cortex Magnoliae officinalis) 10g and Bai Ying 20g. Biography Tai Lahans has been specializing in the treatment of chronic viral diseases and integrative cancer treatment for the past 23 years in Seattle, USA. Her book, Integrating Conventional and Chinese Medicine in Cancer Care: A Clinical Guide, was published in 2007. She is currently working on a second book tentatively titled Pathologies of the Modern Cancer Epidemic: How Chinese Medicine Can Help. It is a book on the prevention of cancers.

References

1. Wingo, P.A. Cancer Statistics, 2007. Cancer 2007;45:8-30
2. Miller, B.A. Cancer Statistics Review 1979 – 2008. National Cancer Institute, National Institutes of Health Publication N 92 0 2789; 2008.
3. Burkitt, D.P. Dietology and Prevention of CRC. Hospital Practice 1984;19:67.
4. Maclennan, R. /Dietary fiber, transit time, fecal bacteria, steroids, and colon cancer in two Scandanavian populations: reports from the International Agency for Research in Cancer Intestinal Microecology Group. Lancet 1977; 2:207-211.
5. Zhang Dai Zhao et al. E Xing Zhong Liu Fang Hua Zhong Xi Zhi Liao ( Chinese Materia Medica in the Treatment of Malignant Tumors with Chemotherapy and Radiotherapy ), Beijing: People’s Medical Publishing House, 2000ACE.
6. Cao Guangwen. Xian Dai Zhong Liu Sheng Wu Zhi Liao Xue ( Current Biological Treatment of Tumors ), Beijing: People’s Military Medicine Publishing Press, 1995 ACE.
7. Li Gao. Pi Wei Lun ( A Treatise on the Stomach and Spleen ). 1249 ACE. Many English translations; Shanxi Science and Technology Press, 1986 ACE.
8. Gui Hao. Shi Jing ( The Diet Classic ). Unknown date. Source unavailable; read in library at Beijing Academy of Sciences.
8a. Ji Lin Liu. Chinese Dietary Therapy. Available through Redwing Reviews.
9. Takeshi Sawada. Kaitai Hatsumou. Ido No Nippon Journal. August, 1949.
10. Xue Sheng Bai. Shi Re Tiao Bian ( Systematic Differentiation of Damp Heat ). Qing Dynasty. Joint Publishing company, Hong Kong, 1989.
11. Ippo Okamoto. Shinkyu Azeyoketsu. 1703 ACE. As quoted by Bunshi Shiroda in Shinkyu Chiryo Kisogaku. Unavailable in the USA.
12. Sun Ren Cun. Quan Sheng Zhi Mi Fang ( Guiding Formulas for the Whole Life ). Song Dynasty. Not published in entirety in modern times. Many of these formulas are part of other formularies.
13. Zhang Zhong Jing. Shang Han Za Bing Lun ( Discussion of Cold-Induced Disorders ). 210 ACE. People’s Health Publishing. 1987 ACE. Many translations are available.
14. Han Rui. Zhong Liu Hua Xue Yu Fang Ji Yao Wu Zhi Liao ( Chemical Drugs and Preparations in the Prevention and Treatment of Tumors ). Beijing: Beijing Medical University and Peking Union Medical University Joint Press ), 1992.
15. Cao Guangwen et al. Xian Dai Ai Zheng Sheng Wu Zhi Liao Xue ( Current Biological Treatment of Cancer ). Beijing: People’s Military Press. 1995.
16. Yu Rencun. Immune mechanism of Chinese material medica in inhibiting cancer. Zhong Guo Zhong Liu ( Chinese journal of Oncology ) 1993;2:20-21.
17. Sun Qing Jing. Dan Shen Dui Gan Ai Zheng Sheng wu Liao Xue ( Current Biological Treatment of Cancer ). Beijing. People’s Military Press. 1995;2.
18. Huang Li Zhong. Yuan Fa Xing Gan Ai Zhong Yi Zhi Fa De Lin Chuang Yan Jiu ( Clinical Study of Primary Liver Cancer With Traditional Chinese Medicine Methods ). Hunan Zhong Yi Xue Yuan Xue Bao ( J Hunan TCM College ). 1996; 16:14-17.
19. Zhang Dai Zhao. Zhang Dai Zhao Zhi Ai Jing Yan Ji Yao ( A Collection of Zhang Dai Zhao’s Experiences in the Treatment of Cancer ). Beijing. China Medicine and Pharmaceutical Publishing House. 2001.

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Vitamin D potential for management of brain tumors

Accumulating data have provided evidence that vitamin D is involved in
brain function. Vitamin D can inhibit the synthesis of inducible nitric
oxide synthase and increase glutathione levels, suggesting a role for
the hormone in brain detoxification.

The study shows that vitamin D helps remove mercury from your body
safely by radically increasing the amount of intracellular glutathione.

Neuroprotective and immunomodulatory effects of this hormone have also
been described in several experimental models, indicating the potential
value of vitamin D in helping neurodegenerative and neuroimmune
diseases. In addition, vitamin D induces glioma cell death, making the
hormone of potential interest in the management of brain tumors.

These results reveal previously unsuspected roles for vitamin D in
brain function and suggest possible areas of future research.

Sources:
Trends in Endocrinology and Metabolism April 2002,Volume 13, Issue 3,
1, Pages 100-105

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Role of epigallocatechin gallate (EGCG) in the treatment of breast and prostate cancer

Stuart EC, Scandlyn MJ, Rosengren RJ. Role of epigallocatechin gallate (EGCG) in the treatment of breast and prostate cancer. Life Sci. 2006;79: 2329-2336.

 

Epigallocatechin-3-gallate (EGCG), a major constituent of green tea (Camellia sinensis), has been studied extensively as a potential treatment for many diseases, including various cancers. EGCG has been shown to have beneficial effects on Parkinson’s disease, Alzheimer’s disease, stroke, and diabetes. Epidemiologic data suggest that EGCG may protect against hormone-related cancers, such as breast and prostate cancers. The potential efficacy of EGCG in the treatment of breast and prostate cancers is reviewed and the possible mechanisms of action involved are discussed.

 

 

Several in vitro studies have shown a decrease in the number of both androgen-dependent (LNCaP) and androgen-independent prostate (DU145) cancer cells in response to treatment with EGCG. Apoptosis has been identified as the mechanism responsible for this effect, and the degree of apoptosis after EGCG treatment appears to be similar in DU145 and LNCaP cells. This finding suggests that the cytotoxic effects of EGCG are not influenced by the presence or absence of the androgen receptor. EGCG has also been shown to inhibit the activity of the epidermal growth factor receptor (EGFR) and to reduce the nuclear localization of nuclear factor kB (NF-kB) in prostate cancer cells. EGFR is known to activate intracellular enzymatic pathways that play a role in anti-apoptotic and growth stimulatory signaling. NF-kB is vital for tumor growth because it promotes and represses the expression of genes involved in survival and apoptosis. EGCG also inhibits various processes required for angiogenesis and metastasis in prostate cancer cells.

 

 

Increases in insulin-like growth factor-I (IGF-I) and decreases in IGF-binding protein-3 (IGFB-3) are associated with the progression of prostate cancer and with poor outcomes in prostate cancer patients. Animal studies have shown that the consumption of a green tea mixture containing EGCG decreased IGF-I and increased IGFBP-3 levels. Thus, the modulation of these two molecules may represent a mechanism for chemoprevention via green tea consumption. Relatively few epidemiologic studies of the association between green tea consumption and prostate cancer risk have been conducted, and those that have been conducted have yielded conflicting results. Several clinical trials have been conducted to determine the ability of green tea extracts to prevent the development and progression of prostate cancer. The results of these trials to date indicate that green tea has little antineoplastic ability. The use of caffeinated preparations in trials has limited ability of subjects to complete the experimental treatments. Future trials should employ decaffeinated green tea extract preparations or purified EGCG.

In vitro studies have shown that EGCG is cytotoxic to breast cancer cells, regardless of estrogen receptor status; although, few studies have evaluated the mechanism responsible for this cytotoxicity. However, on the basis of a comprehensive literature review, it is thought likely that EGCG induces apoptosis in most, if not all, breast cancer cell lines by modulating intracellular signaling pathways that control cell cycle progression. Most in vivo studies of the beneficial effects of green tea extracts on breast cancer chemoprevention have used polyphenol mixtures rather than individual catechins. However, both studies of polyphenol mixtures and of EGCG alone have shown beneficial effects on tumor growth and metastases, which suggests that EGCG is predominantly responsible for the chemopreventative effect. Epidemiologic studies of the association between green tea consumption and breast cancer risk have also yielded conflicting results, i.e., some have shown no association and some chemopreventative effects. For example, different studies have shown chemopreventative effects of green tea consumption in specific groups of women, such as those with the low-activity catechol-O-methyltransferase allele, high-activity angiotensin-converting enzyme, or low levels of estrones.

 

The authors conclude that “EGCG induces apoptosis in both breast and prostate cancer cells in vitro.” It appears that the cytotoxic effect of EGCG is not influenced by the hormone receptor status of the cell lines of either of these cancers. The cell cycle of both of these cancer cell lines has been shown to be arrested in the G1 phase after treatment with EGCG. This likely results from a decrease in the auto-phosphorylative capacity of EGFR and the subsequent decrease in activity of intracellular signaling cascades, which are activated by EGFR. Although the authors consider these results to be “promising,” they have yet to be duplicated in in vivo models or in cancer patients.

 

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