Research from the Linus Pauling Institute at Oregon State University suggests that natural compounds of chlorophyll, chlorophyllin, and selenium compounds, which previously have been studied for their ability to preventing a cancerous condition, may be able to play a more significant role in reversing a cancerous condition.
A new study just published in the International Journal of Cancer examined the activity of chlorophyllin and found that, on a dose-by-dose basis, it was 10 times more potent at causing death of colon cancer cells than hydroxyurea, a chemotherapeutic drug commonly used in cancer treatment.
Beyond that, chlorophyllin kills cancer cells by blocking the same phase of cellular division that hydroxyurea does, but by a different mechanism. This suggests that it – and possibly other “cocktails” of natural products – might be developed to have a synergistic effect with conventional cancer drugs, helping them to work better or require less toxic dosages, researchers said.
“We conclude that chlorophyllin has the potential to be effective in the clinical setting, when used alone or in combination with currently available cancer therapeutic agents,” the researchers wrote in their study.
The concept of combining conventional or new cancer drugs with natural compounds that have been shown to have anti-cancer properties is very promising, said Rod Dashwood, professor and director of the Cancer Chemoprotection Program in the Linus Pauling Institute.
“Most chemotherapeutic approaches to cancer try to target cancer cells specifically and do something that slows or stops their cell growth process,” Dashwood said. “We’re now identifying such mechanisms of action for natural compounds, including dietary agents. With further research we may be able to make the two approaches work together to enhance the effectiveness of cancer therapies.”
Chlorophyllin is a water-soluble derivative of chlorophyll – the green pigment found in most plants and many food products that makes possible the process of photosynthesis and plant growth from the sun’s energy. Chlorophyllin is inexpensive, and animal studies plus human clinical data suggest that it can be ingested at relatively high levels without toxicity.
In the new study, researchers found that pharmacologic doses of chlorophyllin caused colon cancer cells to spend more time than normal in their “synthesis phase” in which DNA is duplicated. Timing is critical to the various phases of cell growth, researchers said, and this disruption started a process that ultimately led to cell death, the study found.
In particular, the presence of high levels of chlorophyllin caused a major reduction in the level of ribonucleotide reductase, an enzyme critical to DNA synthesis, researchers found. This is also the mechanism of action of hydroxyurea, one drug already being used for cancer chemotherapy.
“In cancer research right now there’s interest in approaches that can reduce ribonucleotide reductase,” Dashwood said. “At the doses used in our experiments, chlorophyllin almost completely stops the activity of this enzyme.”
Further research is needed both in laboratory and animal studies, with combinations of chlorophyllin and existing cancer drugs, before it would be appropriate for human trials, Dashwood said. Chlorophyllin, in general, is poorly absorbed from the human gastrointestinal tract, so it’s unclear what levels might be needed for therapeutic purposes or how well they would work.
Other dietary agents also might have similar potential. Work just published by LPI researchers in the journals Carcinogenesis and Cancer Prevention Research explored the role of organic selenium compounds in killing human prostate and colon cancer cells. Colorectal and prostate cancers are consistently among the leading causes of cancer mortality in the United States, and will account respectively for 18 percent and 9 percent of all cancer deaths in 2009, according to estimates from the American Cancer Society.
In the recent studies, a form of organic selenium found naturally in garlic and Brazil nuts was converted in cancer cells to metabolites that acted as “HDAC inhibitors” – a promising field of research in which silenced tumor suppressor genes are re-activated, triggering cancer cell death.
“Whether it’s HDAC inhibition leading to one manner of cancer cell growth arrest, or loss of ribonucleotide reductase activity leading to another, as seen with chlorophyllin, there’s significant promise in the use of natural products for combined cancer therapies,” Dashwood said. “These are areas that merit continued research.”
These studies were supported by the National Cancer Institute and the National Institute of Environmental Health Sciences. Other collaborators included researchers from the New York Medical College and the Penn State College of Medicine.
Chlorophyll is identical to your hemoglobin except for the center atom. Dr. Robert O. Young’s, at the pH Miracle Living Center in San Diego, California suggests, “as one increases their consumption of chlorophyll from green foods and green drinks the quality and quantity of the red blood cells improve. This can be noted on a CBC medical test as the red blood cell count increases and the hemoglobin increases to a healthy range. Liquid chlorophyll and chlorophyllin can be added to any water or green drink to improve the concentration of this powerful blood building compound.”
References: Chlorophyll and Chlorophyllin
2. Sudakin DL. Dietary aflatoxin exposure and chemoprevention of cancer: a clinical review. J Toxicol Clin Toxicol. 2003;41(2):195-204. (PubMed)
3. Dashwood RH. The importance of using pure chemicals in (anti) mutagenicity studies: chlorophyllin as a case in point. Mutat Res. 1997;381(2):283-286. (PubMed)
4. Egner PA, Stansbury KH, Snyder EP, Rogers ME, Hintz PA, Kensler TW. Identification and characterization of chlorin e(4) ethyl ester in sera of individuals participating in the chlorophyllin chemoprevention trial. Chem Res Toxicol. 2000;13(9):900-906. (PubMed)
5. 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. 1994;308(2):191-203. (PubMed)
6. 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):211-218. (PubMed)
7. Breinholt V, Schimerlik M, Dashwood R, Bailey G. Mechanisms of chlorophyllin anticarcinogenesis against aflatoxin B1: complex formation with the carcinogen. Chem Res Toxicol. 1995;8(4):506-514. (PubMed)
8. Egner PA, Munoz A, Kensler TW. Chemoprevention with chlorophyllin in individuals exposed to dietary aflatoxin. Mutat Res. 2003;523-524:209-216. (PubMed)
9. Kumar SS, Devasagayam TP, Bhushan B, Verma NC. Scavenging of reactive oxygen species by chlorophyllin: an ESR study. Free Radic Res. 2001;35(5):563-574. (PubMed)
10. Kamat JP, Boloor KK, Devasagayam TP. Chlorophyllin as an effective antioxidant against membrane damage in vitro and ex vivo. Biochim Biophys Acta. 2000;1487(2-3):113-127. (PubMed)
11. 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;542(1-2):89-97. (PubMed)
12. Kumar SS, Shankar B, Sainis KB. Effect of chlorophyllin against oxidative stress in splenic lymphocytes in vitro and in vivo. Biochim Biophys Acta. 2004;1672(2):100-111. (PubMed)
13. Yun CH, Jeong HG, Jhoun JW, Guengerich FP. Non-specific inhibition of cytochrome P450 activities by chlorophyllin in human and rat liver microsomes. Carcinogenesis. 1995;16(6):1437-1440. (PubMed)
14. Dingley KH, Ubick EA, Chiarappa-Zucca ML, et al. Effect of dietary constituents with chemopreventive potential on adduct formation of a low dose of the heterocyclic amines PhIP and IQ and phase II hepatic enzymes. Nutr Cancer. 2003;46(2):212-221. (PubMed)
16. 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 and two heterocyclic amines in the Salmonella mutagenicity assay. Carcinogenesis. 1991;12(5):939-942. (PubMed)
17. Kensler TW, Groopman JD, Roebuck BD. Use of aflatoxin adducts as intermediate endpoints to assess the efficacy of chemopreventive interventions in animals and man. Mutat Res. 1998;402(1-2):165-172. (PubMed)
18. Simonich MT, Egner PA, Roebuck BD, et al. Natural chlorophyll inhibits aflatoxin B1-induced multi-organ carcinogenesis in the rat. Carcinogenesis. 2007;28(6):1294-1302. (PubMed)
19. Breinholt V, Hendricks J, Pereira C, Arbogast D, Bailey G. Dietary chlorophyllin is a potent inhibitor of aflatoxin B1 hepatocarcinogenesis in rainbow trout. Cancer Res. 1995;55(1):57-62. (PubMed)
20. 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 Carcinog. 2006;5:6. (PubMed)
21. 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;3(1):3-10. (PubMed)
22. Egner PA, Wang JB, Zhu YR, et al. Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer. Proc Natl Acad Sci U S A. 2001;98(25):14601-14606. (PubMed)
23. Chernomorsky SA, Segelman AB. Biological activities of chlorophyll derivatives. N J Med. 1988;85(8):669-673. (PubMed)
24. Siegel LH. The control of ileostomy and colostomy odors. Gastroenterology. 1960;38:634-636. (PubMed)
26. Christiansen SB, Byel SR, Stromsted H, Stenderup JK, Eickhoff JH. [Can chlorophyll reduce fecal odor in colostomy patients?]. Ugeskr Laeger. 1989;151(27):1753-1754. (PubMed)
27. Young RW, Beregi JS, Jr. Use of chlorophyllin in the care of geriatric patients. J Am Geriatr Soc. 1980;28(1):46-47. (PubMed)
28. 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;74(22):2739-2747. (PubMed)
33. Smith RG. Enzymatic debriding agents: an evaluation of the medical literature. Ostomy Wound Manage. 2008;54(8):16-34. (PubMed)
34. Weir D, Farley KL. Relative delivery efficiency and convenience of spray and ointment formulations of papain/urea/chlorophyllin enzymatic wound therapies. J Wound Ostomy Continence Nurs. 2006;33(5):482-490. (PubMed)
36. GPO Access. Electronic Code of Federal Regulations: Miscellaneous Internal Drug Products for Over the Counter Use. [Web page]. Available at: http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?c=ecfr&sid=
21:18.104.22.168.27.5&idno=21. Accessed June 4, 2009.
37. GPO Access. Electronic Code of Federal Regulations: Listing of Color Additives Exempt from Certification [Web page]. Available at: http://ecfr.gpoaccess.gov/cgi/t/text/text-idx?c=ecfr&sid=
21:22.214.171.124.126.96.36.199&idno=21. Accessed June 4, 2009.
39. Smith LW. The present status of topical chlorophyll therapy. N Y State J Med. 1955;55(14):2041-2050. (PubMed)
40. Gogel HK, Tandberg D, Strickland RG. Substances that interfere with guaiac card tests: implications for gastric aspirate testing. Am J Emerg Med. 1989;7(5):474-480. (PubMed)