Protect Yourself From Environmental Cancer

Cancer is the second leading cause of death in the United States, accounting for one out of every four deaths.¹ Researchers estimate that lifestyle and environmental factors may contribute to approximately 90% of cancer cases!^2,3

On a daily basis, we are exposed to a rapidly growing list of carcinogens in the environment. The sources of these carcinogens range from cigarette smoke and cooked meat to pesticides and plastic packaging.^3,4-7 These chemicals damage DNA and disrupt proper cell communication,^8,9 potentially leading to tumor formation.

With contamination of our food, air, and water, it’s impossible to completely avoid environmental carcinogens.^10,11 The best course of action is to arm ourselves with something that can neutralize the carcinogens, thereby protecting our DNA and ultimately preventing cancer.

Scientists have studied and identified an effective neutralizer in chlorophyllin, a substance derived from chlorophyll, the pigment in plants that gives them their green color.

In this article, you will learn how chlorophyllin protects your body from cancer-causing agents, promotes growth of healthy cells, and acts as a potential co-therapeutic agent to improve treatment and health in cancer patients.

How Chlorophyllin Works

Chlorophyllin’s special cancer-fighting properties stem from its ability to bind to mutagenic substances and excrete them from the body before they can do any damage.¹² In fact, a study reported in the Journal of Toxicology and Environmental Health reported that chlorophyllin binds to certain mutagens 20 times better than resveratrol.¹³

Carcinogens interfere with normal cell growth by binding to DNA and creating DNA adducts, which are pieces of DNA bonded to a cancer-causing chemical. Evidence in laboratory animals shows that these adducts contribute to cancer by causing extensive and irreversible DNA damage.^14,15

Chlorophyllin helps protect against cancer by attaching itself to and degrading these damaging substances,¹⁶ which prevents them from inducing mutations in DNA.¹⁷ In this way, chlorophyllin acts as an interceptor molecule by isolating carcinogens so that they cannot form dangerous DNA adducts.

Potent Cancer Inhibitor

 

Studies in both animals and humans demonstrate chlorophyllin’s ability to bind to carcinogens and remove them from the body.

Rainbow trout have been used for over 40 years as an experimental model for testing the effects of environmental factors on cancer.^18,19 In one recent study, researchers found that chlorophyllin stopped the formation of tumors in the stomach and liver of trout that had been induced by a leading cancer-causing agent known as DBP (dibenzo[a,l]pyrene).²⁰ DBP, a compound found in cigarette smoke and coal tar, is one of the most potent environmental carcinogens known.²¹

In this study, chlorophyllin reduced the amount of DBP in the liver by up to 63%. The researchers attribute these findings to chlorophyllin’s remarkable ability to bind to DBP in cell culture and suggest that chlorophyllin has cancer-preventing properties across multiple organs.

Evidence suggests these potent anticancer properties of chlorophyllin are also beneficial in humans. In a recent study, researchers fed human subjects a diet containing meat cooked at a high temperature (i.e. full of carcinogens).²² When researchers added cancer inhibitors—a combination of chlorophyllin tablets, cruciferous vegetables, and yogurt—to the diet, the subjects’ bodies excreted more of the damaging compounds through their urine and feces compared to when they ate the meat without the inhibitors.

Furthermore, the inhibitors also reduced DNA damage in colorectal cells cultured in a dish by nearly two-fold! The authors indicate that studying the effects of each of the inhibitors separately will help clarify the degree to which chlorophyllin protects the cells against DNA damage.²²

What You Need To Know

Chlorophyllin Protects Against Environmental Carcinogens

• Carcinogens cause DNA damage that can lead to the formation of tumors.
• Chlorophyllin protects healthy cells from DNA damage by binding to carcinogens and increasing their removal from the body.
• In addition, chlorophyllin inhibits the growth of cancer cells, reduces oxidative damage, supports the immune system, and can boost the effectiveness of cancer drugs.
• The photosensitizing effects of chlorophyllin make it a viable low-cost agent to use in photodynamic therapy, a new treatment for small, local tumors near the surface of the skin or internal organ lining.

Chlorophyllin Protects Against Liver Damage

Chlorophyllin’s DNA-protecting mechanisms have been studied extensively in relation to a fungal toxin known as AFB1 (aflatoxin B1). This “natural” contaminant is abundant in corn, peanuts, soy sauce, fermented soy beans, and other food crops grown in sub-Saharan African and Asian countries, and is one of the most carcinogenic substances known.^23-25

When these contaminated foods are eaten, AFB1 is broken down in the liver to a deadly carcinogenic product that binds to and mutates DNA.^26-28This drastically increases the risk of a specific type of liver cancer called hepatocellular carcinoma, especially in individuals with hepatitis B.^29,30

To determine if chlorophyllin’s “interceptor” role could help protect against liver cancer, scientists studied individuals living in the Qidong region of China.³¹ Here, residents are unavoidably exposed to high AFB1 levels, and suffer high mortality rates due to liver cancer.^31,32

When individuals took 100 mg of chlorophyllin three times per day before meals for three months, it led to a 55% decrease in the levels of a urine compound (aflatoxin-N7-guanine) that indicates AFB1-induced DNA damage, compared to individuals who took a placebo.^12,31 Previous research has indicated that levels of this urine compound are also highly associated with liver cancer risk.²⁹

The scientists didn’t stop there. They dug deeper to prove whether chlorophyllin directly inhibited AFB1 absorption into the body. To determine this, they gave four human volunteers a low dose (30 ng) of AFB1 that had been labeled with a radioactive “tag” to track the chemical’s path, and then took blood and urine samples for 72 hours.²⁹

When the volunteers took a 150 mg dose of chlorophyllin along with the AFB1, AFB1 absorption rate into the bloodstream decreased drastically and the urine output of the AFB1-induced DNA damage compound was reduced. Although more volunteers need to be tested to confirm these results, these data further support the hypothesis that chlorophyllin reduces AFB1 absorption by the body.³³

Once scientists knew that chlorophyllin could reduce the absorption of AFB1, they took the research a step further to find out if the protective effects of chlorophyllin against DNA damage would contribute to reduced liver tumor formation.

In order to determine this, researchers gave rats AFB1 plus chlorophyllin (250 mg/kg body weight) five times per day for three days, while other rats were given AFB1 plus a placebo.³⁴ Compared to rats given AFB1 and a placebo, the rats given AFB1 along with chlorophyllin had a 42% reduction in liver DNA adducts and a 137% increase in fecal AFB1 content, further indicating that chlorophyllin increases the AFB1 excretion from the body to reduce DNA damage.

Furthermore, the study found that giving this amount of chlorophyllin to the exposed rats for 10 days reduced AFB1-induced precancerous lesions in the liver as well as in the colon. All of this points to the fact that chlorophyllin protects these vital organs and reduces tumor formation by increasing the removal of this toxic chemical from the body.³⁴

However, it’s important to note that when chlorophyllin was given after AFB1-induced liver cancer was initiated, it did not significantly inhibit tumor progression in one study,³⁵ suggesting the effects of chlorophyllin may be stronger when it is given earlier in the tumor-initiating process.

Chlorophyllin Inhibits The Growth Of Some Cancer Cells

We’ve already seen that chlorophyllin can protect against cancer by binding to and eliminating harmful carcinogens from the body. In addition, chlorophyllin has been found to inhibit the growth of cancer cells through three important mechanisms:

1. Chlorophyllin may be able to halt the proliferation of deadly tumors specifically by inducing the death of cancerous cells. A study published in Cancer Research found that treating human colon cancer cells with various concentrations (0.0625-0.5 mM) of chlorophyllin for 24 hours promoted “cell suicide” (apoptosis) in these cells by interacting with “death receptors” on the membrane surface of cancer cells.³⁶ Chlorophyllin is generally nontoxic in normal tissue,^37,38 and researchers observed that chlorophyllin may be able to selectively trigger death in cancer cells while maintaining normal cell growth.³⁹
2. Chlorophyllin helps prevent cancer cells from spreading (metastasis). In a study of cultured human colon cancer cells, researchers determined that chlorophyllin increases the expression of a protein called E-cadherin, which coordinates cell growth by allowing the cells to communicate with one another.^36,40 High levels of E-cadherin are important for decreasing cancer-cell invasion and metastasis,⁴⁰ as dysfunction of E-cadherin inhibits cell-to-cell communication and was linked with uncontrolled cell growth.^41,42
3. Chlorophyllin helps reduce tumor formation. It does this by inhibiting angiogenesis, the process of developing new blood vessels from existing ones, which increases oxygen and nutrient delivery to tumors.⁴³ The increase in blood vessel formation promotes the dangerous, possibly deadly spread of tumor cells throughout the body.⁴⁴ In a hamster model of oral cancer, a daily dose of 4 mg/kg body weight of chlorophyllin for 14 weeks reduced the expression of several proteins involved in angiogenesis in the cheek pouches of the animals.⁴⁵ In this study, the lower content of angiogenesis proteins was also associated with reduced tumor formation in the hamster cheek pouches, further indicating the compound’s ability to halt the progression of cancer by mitigating tumor-related angiogenesis.

Chlorophyllin Reduces Oxidative Damage

 

Another important way chlorophyllin helps prevent cancer is by helping defend the body against oxidative damage caused by free radicals. Like the smoke from a fire, free radicals are a byproduct that our bodies produce when we burn fuel for energy. They also come from environmental pollutants, radiation, and chemical agents. Although your body has natural defense systems in place to eliminate these harmful free radicals, excessive free-radical production overwhelms these defense systems, leading to extensive DNA damage that causes cancer.⁴⁶

Research has shown that chlorophyllin is capable of scavenging a wide variety of reactive oxygen species (a type of free radical containing oxygen).⁴⁷ Furthermore, a recent study in cultured liver cancer cells⁴⁸ showed that chlorophyllin was one of the most potent inducers of a set of enzymes that protect the cells against potentially harmful oxidants and electrophiles, two types of unstable molecules that damage tissues and contribute to cancer.^49,50

One way free radicals cause damage to cells is through DNA strand breakage. If the DNA has too many strand breakages and/or if the repair mechanisms are insufficient or defective, abnormal cell growth—and ultimately, cancer—can occur as a result.⁵¹ Studies show that chlorophyllin plays an important role in reducing this dangerous DNA strand breakage.

In one study, chlorophyllin was found to reduce DNA strand breakage induced by oxidative stress in calf thymus DNA.⁵² In another study, 18 weeks of chlorophyllin treatment reduced tumor formation and enzyme activity associated with oxidative stress and inflammation in mouse skin treated with a carcinogen, further supporting the link between chlorophyllin’s free-radical fighting and antitumor properties.⁵³

Another way excessive free radicals cause damage is by destroying white blood cells called lymphocytes. Since the job of lymphocytes is to protect your body against cancerous cells and potentially damaging foreign organisms, destroying them reduces your body’s ability to fight cancer.²

Researchers found that injecting chlorophyllin into mice that had undergone whole-body radiation prevented the unnecessary death of these immune system cells by reducing the production of reactive oxygen species in the lymphocytes from their spleen.⁵⁴

Chlorophyllin’s Anticancer Powers

Special properties in chlorophyllin’s unique molecular structure allow it to protect vital organs from damage through a variety of mechanisms. Research has shown that chlorophyllin’s anticancer powers include:

• Complex formation with carcinogens, thereby protecting healthy cells from DNA damage.^17,33,34,66
• Promotion of healthy cell growth by supporting the destruction and “clean-up” of cancerous cells, preventing them from spreading throughout the body and damaging vital organs.^36,40,45
• Ability to scavenge various free radicals, highly reactive molecules that cause the oxidative damage that is associated with cancer development.^31,47,52,54
• Photosensitive properties that may make it a valuable therapeutic option for treating certain cancers through photodynamic therapy.^60,61
• Potential ability to treat leukopenia, a symptom of some cancers and common side effect of cancer treatment.⁶²
• Improvements in the efficacy of the cancer drug oxaliplatin in cell culture, even in drug-resistant cancer cells.⁶⁵

Photosensitizing Effects Of Chlorophyllin

Photodynamic therapy is an exciting new cancer treatment typically used for small, local tumors⁵⁵ on or just under the skin, or on the lining of internal organs and cavities, such as the bladder.^56-58 The therapy involves injecting into the bloodstream an agent called a photosensitizer, which is sensitive to a particular type and wavelength of light.⁵⁷

Although the photosensitizer is absorbed by both normal and cancerous cells, it stays in cancer cells longer than in normal cells. Exposing the tumor to light about 24 to 72 hours after injection will preferentially destroy tumor cells and minimize exposure to normal cells.^57,59

Recent research suggests that the remarkable photosensitizing properties of chlorophyllin make it a low-cost option for this novel therapy. In two studies, scientists recently synthesized two forms of chlorophyllin called chlorophyllin e4 and chlorophyllin f and discovered that using these forms in photodynamic therapy increased the death of human bladder cancer cells in cell culture.^60,61 Further research from these scientists showed that using photodynamic therapy with chlorophyllin f in two types of cultured human bladder cancer cells induced the death of approximately 85% of the cancer cells.^60,61

Leukopenia (low white blood cell count) is a symptom of some types of cancer, such as Hodgkin’s lymphoma, and may be an undesired side effect of cancer treatments such as chemotherapy and radiation therapy. Because white blood cells are critical for immune function, leukopenia weakens the immune system and makes the body vulnerable to infection and illness.^62,63

One study indicated that chlorophyllin might help treat leukopenia and thereby help maintain immune system function. For the study, researchers gave three 40 mg sodium copper chlorophyllin tablets per day for one month to patients with leukopenia caused by various factors. The chlorophyllin was effective in treating 85% of patients and was significantly more effective than placebo tablets and similar to Leucogen^® tablets, a drug sometimes used to treat leukopenia.⁶²

Chlorophyllin: An Explanation

What Is Chlorophyllin?

• Chlorophyllin is a semi-synthetic mixture of sodium copper salts derived from chlorophyll,³¹ the naturally occurring green pigment that gives plants and algae their color and helps plants trap light needed for photosynthesis.

What Is The Difference Between Chlorophyll And Chlorophyllin?

• Although both chlorophyll and chlorophyllin have a ring-like structure, chlorophyll has a magnesium molecule at the center of the ring and a chain of carbon and hydrogen molecules.⁶⁷ Chlorophyllin typically has copper at the center of its ring and does not have the chain of carbon and hydrogen molecules.⁶⁸
• Because chlorophyllin does not have this carbon/hydrogen chain, it is soluble (dissolves easily) in water, whereas chlorophyll is soluble in fat and insoluble in water.
• The slight variations in molecular structure may allow chlorophyllin to bind particularly effectively with certain carcinogenic molecules and heterocyclic amines.^16,17,69-71 Interestingly, chlorophyllin inhibits the polycyclic aromatic hydrocarbon, benzopyrene, indirectly without binding to the carcinogen.¹⁶

What Else Is Chlorophyllin Used For Besides Cancer Prevention/Treatment?

• Chlorophyllin has been used for over 50 years to reduce fecal^72-74 and urinary⁷⁵ odors.
• According to uncontrolled studies in the 1940s and 1950s,^76,77 it can promote healing of inflamed open wounds due to its antimicrobial properties.
• More recently, chlorophyllin has also been used as an environmentally friendly way to decontaminate food surfaces^78,79 and extend shelf life of food such as strawberries.⁸⁰

Chlorophyllin Assists In Cancer Treatment

Another benefit of chlorophyllin is its ability to boost the effectiveness of cancer drugs.

Oxaliplatin is a moderately effective anticancer drug, although its unpleasant side effects, such as nausea, vomiting, and nerve damage, may limit a person’s ability to take the drug long term.⁶⁴ Additionally, some tumors are resistant to the drug, limiting its effectiveness in combating the cancer.⁶⁵

However, one study indicated that administering chlorophyllin four hours after oxaliplatin increased the drug’s effectiveness in cultured drug-resistant and nonresistant human ovarian cancer cell lines.⁶⁵ Although these effects have yet to be tested in humans, these results support chlorophyllin’s potential, not only in protecting the body against cancer-causing agents, but also as a co-therapeutic agent for cancer drug treatment.

Summary

Researchers estimate that lifestyle and environmental factors may contribute to approximately 90% of cancer cases. These carcinogens damage DNA and can lead to the formation of cancerous tumors. Unfortunately, it’s practically impossible to avoid environmental carcinogens—but what you can avoid is their harmful impact on your body.

Chlorophyllin’s unique molecular structure allows it to act as an “interceptor molecule” that binds to the harmful carcinogens and excretes them from the body before they can damage your DNA.

In addition, chlorophyllin has been found to inhibit the growth of cancer cells, reduce excessive oxidative damage that can lead to cancer, support the immune system, and boost the effectiveness of cancer drugs.

Chlorophyllin’s ability to bind to carcinogens and excrete them from the body before causing DNA damage makes it a safe and low-cost way of protecting against unavoidable environmental carcinogens.

If you have any questions on the scientific content of this article, please call a Life Extension^® Wellness Specialists at 1-866-864-3027.

Editor's Note

Science continues to evolve, and new research is published daily. As such, we have a more recent article on this topic: Protect Against DNA Damage

References

1. Available at: http://www.cdc.gov/cancer/dcpc/data/types.htm. Accessed June 20, 2014.
2. Albert B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. The Preventable Causes of Cancer. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002.
3. Anand P, Kunnumakara AB, Sundaram C, et al. Cancer is a preventable disease that requires major lifestyle changes. Pharm Res. Sep 2008; 25(9):2097–116.
4. Alavanja MC. Introduction: pesticides use and exposure extensive worldwide. Rev Environ Health. 2009 Oct-Dec;24(4):303-9.
5. Brandt-Rauf PW, Li Y, Long C, Monaco R, Kovvali G, Marion MJ. Plastics and carcinogenesis: The example of vinyl chloride. J Carcinog. 2012;11:5.
6. Brophy JT, Keith MM, Watterson A, Park R, Gilbertson M, Maticka-Tyndale E. Breast cancer risk in relation to occupations with exposure to carcinogens and endocrine disruptors: a Canadian case-control study. Environ Health. 2012 Nov 19;11:87.
7. Koutros S, Cross AJ, Sandler DP, et al. Meat and meat mutagens and risk of prostate cancer in the Agricultural Health Study. Cancer Epidemiol Biomarkers Prev. Jan 2008; 17(1):80-7.
8. Chen F, Shi X. Intracellular signal transduction of cells in response to carcinogenic metals. Crit Rev Oncol Hematol. 2002 Apr;42(1):105-21.
9. Hendriks G, van de Water B, Schoonen W, Vrieling H. Cellular-signaling pathways unveil the carcinogenic potential of chemicals. J Appl Toxicol. 2013 Jun;33(6):399-409.
10. Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA. Environmental and chemical carcinogenesis. Semin Cancer Biol. 2004 Dec;14(6):473-86.
11. Eder E, Budiawan, Schuler D. Crotonaldehyde: a carcinogenic and mutagenic air, water and food pollutant. Cent Eur J Public Health. 1996;4 Suppl:21-2.
12. Egner PA, Munoz A, Kensler TW. Chemoprevention with chlorophyllin in individuals exposed to dietary aflatoxin. Mutat Res. Feb-Mar 2003;523-524:209-16.
13. Osowski A, Pietrzak M, Wieczorek Z, Wieczorek J. Natural compounds in the human diet and their ability to bind mutagens prevents DNA-mutagen intercalation. J Toxicol Environ Health, Part A. 2010;73 (17-18):1141–9.
14. Sugimura T, Wakabayashi K, Nakagama H, Nagao M. Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish. Cancer Sci. Apr 2004;95(4):290-9.
15. Cross AJ, Sinha R. Meat-related mutagens/carcinogens in the etiology of colorectal cancer. Environ Mol Mutagen. 2004;44(1):44-55.
16. Tachino N, Guo D, Dashwood WM, Yamane S, Larsen R, Dashwood R. Mechanisms of the in vitro antimutagenic action of chlorophyllin against benzo[a]pyrene: studies of enzyme inhibition, molecular complex formation and degradation of the ultimate carcinogen. Mutat Res. Jul 16 1994;308(2):191-203.
17. Dashwood R, Yamane S, Larsen R. Study of the forces of stabilizing complexes between chlorophylls and heterocyclic amine mutagens. Environ Mol Mutagen. 1996;27(3):211-8.
18. Williams DE. The rainbow trout liver cancer model: response to environmental chemicals and studies on promotion and chemoprevention. Comp Biochem Physiol. Jan 2012;155(1):121-7.
19. Bailey GS, Williams DE, Hendricks JD. Fish models for environmental carcinogenesis: the rainbow trout. Environmental health perspectives. Mar 1996;104 Suppl 1:5-21.
20. Simonich MT, McQuistan T, Jubert C, et al. Low-dose dietary chlorophyll inhibits multi-organ carcinogenesis in the rainbow trout. Food Chem Toxic. Mar 2008;46(3):1014-24.
21. Available at: http://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+4029. Accessed September 29, 2014.
22. Shaughnessy DT, Gangarosa LM, Schliebe B, et al. Inhibition of fried meat-induced colorectal DNA damage and altered systemic genotoxicity in humans by crucifera, chlorophyllin, and yogurt. PloS one. 2011;6(4):e18707.
23. Hudler GW. Magical Mushrooms, Mischievous Molds: The Remarkable Story of the Fungus Kingdom and Its Impact on Human Affairs. Princeton University Press. 1998.
24. Xie F, Lai W, Saini J, Shan S, Cui X, Liu D. Rapid pretreatment and detection of trace aflatoxin B1 in traditional soybean sauce. Food Chem. 2014 May 1;150:99-105.
25. Henry SH, Bosch FX, Bowers JC. Aflatoxin, hepatitis and worldwide liver cancer risks. Adv Exp Med Biol. 2002;504:229-33.
26. Breinholt V, Hendricks J, Pereira C, Arbogast D, Bailey G. Dietary chlorophyllin is a potent inhibitor of aflatoxin B1 hepatocarcinogenesis in rainbow trout. Can Res. Jan 1 1995;55(1):57-62.
27. Jeannot E, Boorman GA, Kosyk O, et al. Increased incidence of aflatoxin B1-induced liver tumors in hepatitis virus C transgenic mice. Int J Cancer . 2012 Mar 15;130(6):1347-56.
28. Kamdem LK, Meineke I, Gödtel-Armbrust U, Brockmöller J, Wojnowski L. Dominant contribution of P450 3A4 to the hepatic carcinogenic activation of aflatoxin B1. Chem Res Toxicol. 2006 Apr;19(4):577-86.
29. Qian GS, Ross RK, Yu MC, et al. A follow-up study of urinary markers of aflatoxin exposure and liver cancer risk in Shanghai, People’s Republic of China. Cancer Epidemiol Biomarkers Prev. 1994 Jan-Feb;3(1):3-10.
30. Ross RK, Yuan JM, Yu MC, et al. Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma. Lancet. Apr 18 1992;339(8799):943-6.
31. Egner PA, Wang JB, Zhu YR, et al. Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer. Proc Nat Acad Sci. 2001 Dec;98(25):14601-6.
32. Yu SZ. Primary prevention of hepatocellular carcinoma. J Gastroenterol Hepatol. 1995;10(6):674-82.
33. Jubert C, Mata J, Bench G, et al. Effects of chlorophyll and chlorophyllin on low-dose aflatoxin B(1) pharmacokinetics in human volunteers. Cancer Prev Res. 2009 Dec;2(12):1015-22.
34. Simonich MT, Egner PA, Roebuck BD, et al. Natural chlorophyll inhibits aflatoxin B1-induced multi-organ carcinogenesis in the rat. Carcinogenesis. 2007 Jun;28(6):1294-1302.
35. Orner GA, Roebuck BD, Dashwood RH, Bailey GS. Post-initiation chlorophyllin exposure does not modulate aflatoxin-induced foci in the liver and colon of rats. J Carcinogenesis. 2006;5:6.
36. Diaz GD, Li Q, Dashwood RH. Caspase-8 and apoptosis-inducing factor mediate a cytochrome c-independent pathway of apoptosis in human colon cancer cells induced by the dietary phytochemical chlorophyllin. Cancer Res. 2003 Mar 15;63(6):1254-61.
37. Young RW, Beregi JS, Jr. Use of chlorophyllin in the care of geriatric patients. J Am Geriat Soc. 1980 Jan;28(1):46-7.
38. Harrison J. W. E. LSE, Trabin B. The safety and fate of potassium sodium copper chlorophyllin and other copper compounds. J Am Pharm Assoc. 1954;18:722-37.
39. Vasenick DC, de Paula NA, Niwa AM, et al. Evaluation of the effects of chlorophyllin on apoptosis induction, inhibition of cellular proliferation and mRNA expression of CASP8, CASP9, APC and b-catenin. Curr Res J Biol Sci. 2012;4(3):315-22.
40. Carter O, Bailey GS, Dashwood RH. The dietary phytochemical chlorophyllin alters E-cadherin and beta-catenin expression in human colon cancer cells. J Nutr. 2004;134(12 Suppl):3441S-44S.
41. Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009 Apr;9(4):265-73.
42. Stockinger A, Eger A, Wolf J, Beug H, Foisner R. E-cadherin regulates cell growth by modulating proliferation-dependent beta-catenin transcriptional activity. J Cell Biol. 2001 Sep 17;154(6):1185-96.
43. Griffioen AW, Molema G. Angiogenesis: potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation. Pharmacol Rev. 2000 Jun;52(2):237-68.
44. Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol. 2002 Dec;29(6 Suppl 16):15-8.
45. Nagini S, Vidya Priyadarsini R, Veeravarmal V, Mishra R. Chlorophyllin abrogates canonical Wnt/beta-catenin signaling and angiogenesis to inhibit the development of DMBA-induced hamster cheek pouch carcinomas. Cell Oncol. 2012 Oct;35(5):385-95.
46. Dizdaroglu M , Jaruga P, Birincioglu M, Rodriguez H. Free radical-induced damage to DNA: mechanisms and measurement. Free Radic Biol Med. 2002 Jun 1;32(11):1102-15.
47. Kumar SS, Devasagayam TP, Bhushan B, Verma NC. Scavenging of reactive oxygen species by chlorophyllin: an ESR study. Free Radic Res. 2001 Nov;35(5):563-74.
48. Fahey JW, Stephenson KK, Dinkova-Kostova AT, Egner PA, Kensler TW, Talalay P. Chlorophyll, chlorophyllin and related tetrapyrroles are significant inducers of mammalian phase 2 cytoprotective genes. Carcinogenesis. 2005 Jul;26(7):1247-55.
49. Talalay P, Dinkova-Kostova AT, Holtzclaw WD. Importance of phase 2 gene regulation in protection against electrophile and reactive oxygen toxicity and carcinogenesis. Adv Enzyme Regul. 2003;43:121-34.
50. Talalay P. Chemoprotection against cancer by induction of phase 2 enzymes. BioFactors. 2000;12(1-4):5-11.
51. Mills KD, Ferguson DO, Alt FW. The role of DNA breaks in genomic instability and tumorigenesis. Immun Rev. 2003 Aug;194:77-95.
52. Park KK, Park JH, Jung YJ, Chung WY. Inhibitory effects of chlorophyllin, hemin and tetrakis(4-benzoic acid)porphyrin on oxidative DNA damage and mouse skin inflammation induced by 12-O-tetradecanoylphorbol-13-acetate as a possible anti-tumor promoting mechanism. Mutat Res. 2003 Dec 9;542(1-2):89-97.
53. Kim J, Yook JI, Park KK, et al. Anti-promotion effect of chlorophyllin in DMBA-TPA-induced mouse skin carcinogenesis. Anticancer Res. 2000 May-Jun;20(3A):1493-8.
54. Kumar SS, Shankar B, Sainis KB. Effect of chlorophyllin against oxidative stress in splenic lymphocytes in vitro and in vivo. Biochimica Biophysic. 2004 May 3;1672(2):100-11.
55. Capella MA, Capella LS. A light in multidrug resistance: photodynamic treatment of multidrug-resistant tumors. J Biomed Sci. 2003 Jul-Aug;10(4):361-6.
56. Vrouenraets MB, Visser GW, Snow GB, van Dongen GA. Basic principles, applications in oncology and improved selectivity of photodynamic therapy. Antican Res. 2003 Jan-Feb;23(1B):505-22.
57. Dolmans DE, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nat Rev Cancer. 2003 May;3(5):380-7.
58. Manyak MJ, Ogan K. Photodynamic therapy for refractory superficial bladder cancer: long-term clinical outcomes of single treatment using intravesical diffusion medium. J Endourol. 2003 Oct;17(8):633-9.
59. Hornung R, Walt H, Crompton NE, Keefe KA, Jentsch B, Perewusnyk G, Haller U, Köchli OR. m-THPC-mediated photodynamic therapy (PDT) does not induce resistance to chemotherapy, radiotherapy or PDT on human breast cancer cells in vitro. Photochem Photobiol. 1998 Oct;68(4):569-74.
60. Li B, Wu Z, Li W, et al. Chlorophyllin e4 is a novel photosensitizer against human bladder cancer cells. Oncol Rep. 2012 May;27(5):1455-60.
61. Lihuan D, Jingcun Z, Ning J, et al. Photodynamic therapy with the novel photosensitizer chlorophyllin f induces apoptosis and autophagy in human bladder cancer cells. Laser Surg Med. 2014 Apr;46(4):319-34.
62. Gao F, Hu XF. Analysis of the therapeutic effect of sodium copper chlorophyllin tablet in treating 60 cases of leukopenia. Chin J Integrat Med. 2005 Dec;11(4):279-82.
63. Ivanov SD, Korytova LI, Yamshanov VA, Ilyin NV, Sibirtsev VS. Leukopenia prognosis during radiation therapy in patients with Hodgkin’s disease. J Exp Clin Cancer Res. 1997 Dec;16(4):413-8.
64. Wafai L, Taher M, Jovanovska V, Bornstein JC, Dass CR, Nurgali K. Effects of oxaliplatin on mouse myenteric neurons and colonic motility. Front Neurosci. 2013 Mar 12;7:30.
65. Yunos NM, Beale P, Yu JQ, Huq F. Synergism from the combination of oxaliplatin with selected phytochemicals in human ovarian cancer cell lines. Anticancer Res. 2011 Dec;31(12):4283-9.
66. Dashwood R, Negishi T, Hayatsu H, Breinholt V, Hendricks J, Bailey G. Chemopreventive properties of chlorophylls towards aflatoxin B1: a review of the antimutagenicity and anticarcinogenicity data in rainbow trout. Mut Res. 1998 Mar 20;399(2):245-53.
67. Chen M. Chlorophyll modifications and their spectral extension in oxygenic photosynthesis. Annu Rev Biochem. 2014;83:317-40.
68. Miret S, Tascioglu S, van der Burg M, Frenken L, Klaffke W. In vitro bioavailability of iron from the heme analogue sodium iron chlorophyllin. J Agric Food Chem. 2010 Jan 27;58(2):1327-32.
69. Dashwood RH, Breinholt V, Bailey GS. Chemopreventive properties of chlorophyllin: inhibition of aflatoxin B1 (AFB1)-DNA binding in vivo and anti-mutagenic activity against AFB1 andtwo heterocyclic amines in the Salmonella mutagenicity assay. Carcinogenesis. May 1991;12(5):939-42.
70. Dashwood R, Guo D. Antimutagenic potency of chlorophyllin in the Salmonella assay and its correlation with binding constants of mutagen-inhibitor complexes. Environ Mol Mutagen. 1993;22(3):164.
71. Dashwood R, Guo D. Protective properties of chlorophylls against the covalent binding of heterocyclic amines to DNA in vitro and in vivo. Princess Takamatsu Symp. 1995;23:181-9.
72. Chernomorsky SA, Segelman AB. Biological activities of chlorophyll derivatives. J Med Society NJ. 1988 Aug;85(8):669-73.
73. Weingarten M, Payson B. Deodorization of colostomies with chlorophyll. Rev Gastroent. 1951 Aug;18(8):602-4.
74. Young RW, Beregi JS Jr. Use of chlorophyllin in the care of geriatric patients. J Am Geriatr Soc. 1980 Jan;28(1):46-7.
75. Yamazaki H, Fujieda M, Togashi M, et al. Effects of the dietary supplements, activated charcoal and copper chlorophyllin, on urinary excretion of trimethylamine in Japanese trimethylaminuria patients. Life Sci. 2004 Apr 16;74(22):2739-47.
76. Bowers WF. Chlorophyll in wound healing and suppurativedisease. Am J Surg. 1947 Jan;73(1):37-50.
77. Carpenter EB. Clinical experiences with chlorophyll preparations with particular reference to chronic osteomyelitis and chronic ulcers. Am J Surg. 1949 Feb;77(2):167-71.
78. Luksiene Z, Paskeviciute E. Microbial control of food-related surfaces: Na-Chlorophyllin-based photosensitization. J Photochem Photobiol. 2011 Oct 5;105(1):69-74.
79. Luksiene Z, Buchovec I, Paskeviciute E. Inactivation of Bacillus cereus by Na-chlorophyllin-based photosensitization on the surface of packaging. J Appl Microbiol. 2010 Nov;109(5):1540-8.
80. Luksiene Z, Paskeviciute E. Novel approach to the microbial decontamination of strawberries: chlorophyllin-based photosensitization. J Appl Microbiol. 2011 May;110(5):1274-83.