Cancer Study Briefs

Cancer Study Briefs

Editors Note: The following study briefs are a special online supplementto the Health Condition Focus on Cancer that appeared in the 7/1/02 issue of INSIDER.

Vitamin Ks Potential Role in Cancer Prevention

Vitamin K, most commonly recognized for its role in blood clotting, may havean additional role in terms of cancer prevention. In vitro research conducted atthe Childrens Hospital of Philadelphia demonstrated that vitamin K inhibitedthe growth of hepatocellular carcinoma cells. Additional in vitro researchindicated that each of three vitamin K analogs dose-dependently inhibited 13different human cancer cell lines.

Sources: Li ZQ et al. Vitamin K uptake in hepatocytes and hepatoma cells.Life Sci. 70(18):2085-100, 2002.

Osada S et al. Tumor cell growth inhibition and extracellularsignal-regulated kinase (ERK) phosphorylation by novel K vitamins. J MolBiol. 314(4):765-72, 2001.

Cause or Not a Cause: Vitamin Ks Possible Link withChildhood Cancer

There has been some concern that vitamin K is involved in causing childhoodcancer, particularly leukemia, as was pointed out by researchers at theUniversity of Bristol, England, in two research papers that were published inthe early 1990s. The researchers suggested that infants receiving vitamin Kinjections at birth were twice as likely to develop leukemia as those who didnot. These hypotheses came to light years after the American Academy ofPediatrics began recommending that newborn babies be given a single,intramuscular dose of .5 to 1 mg of vitamin K to prevent fatalities fromhemorrhagic disease of the newborn (HDN). And, in spite of the findings, theacademy continues to recommend vitamin K injections for newborns because therisk of fatal HDN outweighs the unproven possibility of infant leukemia.

A research review published this year indicated the risk of leukemia fromvitamin K is not convincing based on the evidence at hand. Investigators at theUniversity of Leeds in the United Kingdom conducted a pooled analysis ofindividual patient data from six case-control studies conducted in Great Britainand Germany. Subjects comprised 2,431 children diagnosed with cancer before 15years of age and 6,338 control children. Researchers concluded that while theirstudy means had some flaws in terms of poor data quality, the analysis providedno convincing evidence that intramuscular vitamin K is associated with childhoodleukemia.

Sources: Golding J et al. Factors associated with childhood cancer in anational cohort study. Br J Cancer. 62:304-8, 1990. www.nature.com/bjc.

Golding J et al. Childhood cancer, intramuscular vitamin K, and pethidinegiven during labour. BMJ. 305:341-6, 1992. http://bmj.com.

Roman E et al. Vitamin K and childhood cancer: analysis of individualpatient data from six case-control studies. Br J Cancer. 86(1):63-9, 2002. www.nature.com/bjc.

Glucaric Acid May Prevent Cancer Proliferation

Glucaric acid, which is often bound to minerals to enhance bioavailability,is thought to prohibit cancer growth through a deoxification pathway known asglucuronidation. Nearly all of the published research linking calcium D-glucarate(calcium bound to glucaric acid) to the inhibition of cancer growth andreplication was conducted between the mid-1980s and early 1990s, according to anunpublished research review compiled by a third-party dietitian for Austin,Texas-based Applied Food Sciences, the exclusive distributor of calcium D-glucarate.However, human research is being conductedwith an ongoing Phase I clinical trial--conducted by researchers at theAMC Cancer Research Center in Denver, Colo.--that willelucidate the link between glucaric acid (500 mg/d of calcium D-glucarate) andbreast, lung and prostate cancer.

Glucaric acid bound to potassium has been recently featured in publishedresearch. Investigators from Gifu University School of Medicine in Japan notedthat while calcium D-glucarate was shown to inhibit chemical carcinogenesis invarious animal models, the effect of potassium hydrogen D-glucarate had notbeen fully investigated. They conducted animal research and found that ratssupplemented with potassium hydrogen D-glucarate one week after injection withazoxymethane (a carcinogen) exhibited a 60 percent reduction of tumor incidenceand a 62 percent reduction of tumor multiplicity than the control group, whichwas fed potassium hydrogen carbonate. Researchers concluded that both calcium D-glucarateand potassium hydrogen D-glucarate have potential as natural inhibitors of coloncancer, although more research is necessary.

Source: Yoshimi N et al. Inhibition of azoxymethane-induced rat coloncarcinogenesis by potassium hydrogen D-glucarate. Int J Oncology. 16:43-8,2000.

Chlorophyll Derivitive May Stop Liver Cancer

Chlorophyllin, a water-soluble derivative of chlorophyll, has been suggestedfor reducing the risk of liver cancer. Chlorophyllin was found in an animalmodel to reduce DNA damage from aflatoxin--a cancer-causing agent produced bymold that can infect grains and nuts. For this reason, researchers from theJohns Hopkins Bloomberg School of Public Health and Oregon State Universityfocused a human trial on adults in Qidong, the Peoples Republic of China,because one in 10 there dies of liver cancer due to aflatoxin contamination. Inthe randomized, double blind, placebo-controlled trial, researchers followed 180healthy adults who were randomly assigned to ingest 100 mg of chlorophyllin orplacebo three times daily for four months. Chlorophyllin supplementation induceda 55 percent reduction in median urinary levels of aflatoxin biomarker comparedto placebo. Researchers concluded that chlorophyllin may prevent the developmentof liver cancer or other cancers induced by environmental toxins.

Source: Egner PA et al. Chlorophyllin intervention reduces aflatoxin-DNAadducts in individuals at high risk for liver cancer. PNAS. 98(25):14601-6,2001. www.pnas.org.

Spirulina Extracts May Enhance Immune Function, PreventCancer

Spirulina, which is a blue-green algae, has been named as a possiblechemopreventive agent because of its immune-enhancing activity. Researchers fromthe Osaka Medical Center for Cancer and Cardiovascular Diseases in Japanadministered a hot water extract of Spirulina platensis to subjects andfound that their natural killer cell function was enhanced as compared tocontrol subjects.

Spirulina may offer some degree of protection against certain forms ofcancer through its effect on the immune system, through a direct effect in therepair of DNA, and antioxidant protection from reactive oxygen species generatedduring normal or abnormal metabolism and from toxic substances in theenvironment, wrote Amha Belay, Ph.D., scientific director at Calipatria,Calif.-based Earthrise Nutritionals Inc., in a research review. Furtherresearch along these lines is recommended to validate these assumptions.

Sources: Hirahashi T et al. Activation of the human innate immune systemby Spirulina: augmentation of interferon production and NK cytotoxicity by oraladministration of hot water extract of Spirulina platensis . IntImmunopharm. 2(4):423-34, 2002.

Belay A. The potential application of Spirulina (Arthrospira) as anutritional and therapeutic supplement in health management. JANA. 5(2):27-48,2002. www.americanutra.com.

Resveratrol May Be an Anticarcinogen

Resveratrol is a grape extract found in red wine that has demonstratedanti-carcinogenic effects via several pathways. According to an in vitro studyout of Karol Marcinkowski University of Medical Sciences in Poznan, Poland,resveratrol is protective in all three states of carcinogenesis: initiation,promotion and progression. Researchers at Cook County Hospital in Chicago alsostudied resveratrol with regard to its correlation in the three stages of cancerand concluded that a resveratrol-rich diet may be chemopreventive againstgastric cancer.

Sources: Ignatowicz E, Baer-Dubowska W. Resveratrol, a naturalchemopreventive agent against degenerative diseases. Pol J Pharmacol.53(6):557-69, 2001.

Holian O et al. Inhibition of gastric cancer cell proliferation byresveratrol: role of nitric oxide. Am J Physiol Gastrointest Liver Physiol.282(5):G809-16, 2002.

Garlics Immune-Enhancement May Prove Effective AgainstCancer

Garlic may offer some form of protection against the development of cancerbecause of its immune-enhancing effects. Researchers from Brown UniversityMedical School in Providence, R.I., studied the effects of aged garlic extractson tumor cell migration. Using rat sarcoma tumor cells, researchers found thataged garlic extract inhibited the growth of the cells in a dose-dependentmanner, compared with the number of cells in the control group. The inhibitionof tumor cell migration was also measured, with the average distance in controltrials 7.44 mm, whereas the average distance of cell movement was only 2.48 mmin the highest concentration (20 mg/ml) of aged garlic extract. Researchersconcluded that if tumor cell migration can be slowed, it may be possible tostabilize the tumor in the local area for surgical removal.

There are two compounds derived from garlic that may be the reason behind theherbs protective effects. Allicin has been shown to inhibit the proliferationof several human cancer cell lines, according to researchers from the Universityof Wolverhampton in England. From allicin, ajoene can be derived, whichresearchers studied in relation to human leukemia cells. Ajoene was shown toinhibit proliferation and induce apoptosis in these cells in vitro.

Sources: Hu X et al. Attenuation of cell migration and induction of celldeath by aged garlic extract in rat sarcoma cells. Int J Mol Med. 9(6):641-3,2002.

Ahmed N et al. Ajoene, a garlic-derived natural compound, enhanceschemotherapy-induced apoptosis in human myeloid leukemia CD34-positive resistantcells. Anticancer Res. 21(5):3519-23, 2001.

Red Meat, Gravy Increase Risk of Cancer

Dietary patterns can offer insight into the risk for stomach and esophaguscancers, according to researchers at the Human Nutrition Resaerch Center onAging at Tufts University in Boston. They recruited 124 subjects with esophagealcancer, 124 subjects with distal stomach cancer and 449 control subjects for apopulation-based, case-control study. Dietary analysis indicated that cancer ofthe esophagus was inversely associated with intakes of dairy, fish, allvegetables, citrus fruit and juice, and dark bread, but positively associatedwith gravy intake. Risk of distal stomach cancer was positively associated withred meat intake.

Source: Chen H et al. Dietary patterns and adenocarcinoma of the esophagusand distal stomach. AJCN. 75(1):137-44, 2002. www.ajcn.org.

Broccoli Compound Inhibits Stomach Tumor Formation

Sulforaphane, a compound found in broccoli and broccoli sprouts, was found tokill 3 reference strains and 45 clinical isolates of Helicobacter pylori,a bacteria that is suspected to cause stomach cancer. Researchers from the JohnsHopkins University School of Medicine noted that sulforaphane both inhibited H.Pylori infections and blocked gastric tumor formation in mice.

Source: Fahey JW et al. Sulforaphane inhibits extracellular, intracellularand antibiotic-resistant strains of Helicobacter pylori and preventsbenzo[a]pyrene-induced stomach tumors. PNAS. 99(11):7610-5, 2002. www.pnas.org.

IP-6 Decreases Proliferation of Human Cancer Cells

Inositol hexaphosphate (IP-6) is a naturally occurring substance found inoats, wheat, rice, corn and legumes that has been suggested for chemopreventionbased on its antioxidant properties. Researchers at the Minia School of Medicinein Egypt discovered that IP-6 decreased the proliferation of human breast cancerand colon cancer cell lines by disengaging the cells from normal cycling.

Source: El-Sherbiny YM et al. G0/G1 arrest and S phase inhibition of humancancer cell lines by inositol hexaphosphate (IP6). Anticancer Res.21(4A):2393-403, 2001.

Tea polyphenols Hold Anti-Carcinogenic Promise

The National Foundation for Cancer Research sent out a press release inJanuary 2002 indicating the antioxidant properties of green, black and oolongtea (from Camellia sinensis) are more potent than vitamin C or vitamin Eat protecting cells from oxidative damage that is linked to cancer. Also inJanuary, Rutgers University was awarded a $5.7 million, five-year grant from theNational Cancer Institute to study how tea consumption and diet are linked tocancer.

Research presented at the 93rd annual meeting of the American Association forCancer Research (AACR) detailed how tea polyphenols are involved in cancerprevention. Researchers from the Department of Preventive Medicine at USC/NorrisComprehensive Cancer Center in Los Angeles presented a study involving urinelevels of two tea polyphenol markers--epigallocatechin (EGC) and epicatechin(EC). The investigators found a statistically significant association betweenthe presence of EGC in baseline urine and reduced risk of gastric and esophagealcancer, but no association was found for EC.

Additional tea research presented at the AACR (www.aacr.org)meeting by scientists from the Mayo Clinic and the North Central CancerTreatment Group indicated that green tea therapy is not effective for prostatecancer.  

Melatonin Levels May Indicate Breast Cancer Risk

Decreased melatonin production may be linked with an increased risk of breastcancer, according to researchers at the Fred Hutchinson Cancer Research Centerin Seattle. They compared 813 women diagnosed with breast cancer with 793age-matched control subjects. Subjects who worked graveyard shifts, as well asthose who worked the most nighttime hours, exhibited an increased risk of breastcancer. A similar study conducted by researchers at the Brigham and WomensHospital and Harvard Medical School in Boston. They reviewed the NursesHealth Study, which involved 78,562 women, 2,441 of whom developed breastcancer. Researchers noted that melatonin may have the potential to slow or stoptumor formation.

Source: Davis S et al. Night Shift Work, Light at Night, and Risk ofBreast Cancer. J Nat Cancer Inst. 93(20):1557-62, 2001.

Schernhammer ES et al. Rotating Night Shifts and Risk of Breast Cancer inWomen Participating in the Nurses' Health Study. J Nat Cancer Inst.93(20):1563-8, 2001. http://jncicancerspectrum.oupjournals.org/jnci.

Raspberries Thwart Colon Cancer in Animal Research

Animal research indicated that black raspberries may have a protective effectagainst colon cancer. Rats induced to cancer were fed diets containing 0, 2.5, 5or 10 percent lyophilized black raspberries. Compared to the control group,those animals eating raspberries exhibited reduces aberrations, total tumormultiplicity and a decrease in tumor burden. Researchers concluded it was theantioxidant effects of the berries that induced these results.

Source: Harris GK et al. Effects of lyophilized black raspberries onazoxymethane-induced colon cancer and 8-hydroxy-2-deoxyguanosine levels inthe Fischer 344 rat. Nutr Cancer. 40(2):125-33, 2001. www.erlbaum.com.

Phytosterols May Inhibit Prostate Cancer

Plant phytosterols---sitosterol and campesterol--were found to inhibit thegrowth and metastasis of human prostate cancer cells in research conducted withmice at the State University of New York at Buffalo. The mice fed a mixture ofphytosterols exhibited smaller tumors, half as many lymph node and lungmetastasis as the cholesterol-fed mice, and 60 to 93 percent reduced tumor cellmigration than the control mice. Resaerchers concluded that phytosterolsindirectly and directly inhibit the growth of prostate cancer cells, although -sitosterolwas more protective than campesterol.

Source: Awad AB et al. IN vitro and in vivo (SCID mice) effects ofphytosterols on the growth and dissemination of human prostate cancer PC-3cells. Eur J Cancer Prev. 10(6):507-13, 2001. www.eurjcancerprev.com.

Flavonol, Flavone Intake May Reduce Risk of Lung Cancer inSmokers

An analysis of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study byresearchers at the National Public Health Institute in Helsinki, Finland,indicated that flavonol and flavone intake is inversely associated with the riskof lung cancer in male smokers. Researchers analyzed a study cohort of 27,110male smokers with no history of cancer at baseline. After an average follow-upof 6.1 years, 1,509 cancer cases were diagnosed, 791 of which were lung cancer.Higher intakes of flavonols and flavones seemed to be inversely associated withthe risk of lung cancer, but not with other cancers.

Source: Hirvonen T et al. Flavonol and flavone intake and the risk ofcancer in male smokers (Finland). Cancer Causes Control. 12(9):789-96, 2001. www.kluweronline.com/issn/0957-5243/current.

Amino Acid Combo Helps Underweight Cancer Patients AddFat-Free Mass

A combination of L-arginine, L-glutamine and beta-hydroxy-beta-methylbutyrate(HMB, a metabolite of the essential amino acid leucine,) may reversecancer-related muscle wasting, according to researchers at the Department ofSurgery, Veterans Affair Medical Center, in Reno, Nev. Patients with solidtumors who had lost at least 5 percent body weight were randomly assigned toeither a control group or a treatment group consisting of 14 g/d of L-arginine,14 g/d of L-glutamine and 3 g/d of HMB (as Juven, manufactured by Ames,Iowa-based MTI Biotech). The patients in the treatment group gained morefat-free mass than the control group after a period of four weeks.

Source: May PE et al. Reversal of cancer-related wasting using oralsupplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine,and glutamine. Am J Surgery. 183(4):471-9, 2002. www.elsevier.com/locate/amjsurg.

Curcumin Acts as Antioxidant, May Be Anticarcinogen

Researchers at the Singapore General Hospital and the National University ofSingapore discovered through in vitro research that curcumin, a compoundisolated from the spice turmeric, possesses antioxidant effects that may lend toits anticarcinogenic and anti-inflammatory properties.

Source: Phan TT et al. Protective effects of curcumin against oxidativedamage on skin cells in vitro: its implications for wound healing. J Trauma.51(5):927-31, 2001. www.jtrauma.com.