Kathy Abascal, B.S, J.D., and Eric Yarnell, N.D.

M ost practitioners find it diffi-cult to access, read, and digestcancer research in the midst of

maintaining busy practices. Moreover,the type of investigation many practi-tioners yearn for—studies evaluating thebenefit of whole herbs and foods onbreast cancer prognosis—generally don o t e x i s t . I n s t e a d , mo s t r e s e a r c hexp lores the ef fects of isolated con-stituents on tumor induction in mice,rats, or in vitro. It is almost impossibleto extrapolate with any scientific hon-esty whether whole plants containingthese constituents will reverse, delay, orotherwise mitigate breast cancer pro-gression in women. Nonetheless , it isour hope that a digestible review of thisresearch will help practitioners to findnovel and more effective uses for herbsand foods as adjuncts in breast-cancertherapy.

This article covers the role of seaweeds(also known as sea vegetables), Rosmari-nus officinalis (rosemary), and Panax quin-quefolium (American ginseng) in breastcancer. Each of these plants contains con-stituents that have shown ant itumoreffects, and several of them appear toenhance the effectiveness of various typesof chemotherapy. Each of the plants isnontoxic, and all but American ginsenghave a long history of use in the humandiet. Interestingly, these plants are notcommonly used for breast cancer in folkmedicine but, based on available research,should be considered for use in thatarena.

Seaweeds

Seaweeds attracted interest after epi-d em i o l o g i c s t u d i e s s h owe d t h a tJapanese women had a lower incidenceof breast cancer than Western womenand that Japanese women whose dietscontained more seaweed had the lowestbreast-cancer incidence. According to areview article, the Japanese have a com-paratively high average urinary iodineconcentration (3400 mcg per day) com-pared to Americans (209 mcg per day),which has been attributed to dietaryuse of seaweeds in soups, salads, andsushi, and as a powdered condiment.Nori (Porphyra spp.), wakame (Undariaspp.), and kombu (Laminaria spp.) aresome of the most popular seaweed vari-e t i e s , and i t i s e s t im a t ed t ha t th eJapanese eat an average of 7.9 g of sea-weed daily, most often as stock in misosoup.1

Iodine has been studied for its protec-tive benefit in breast cancer.2 Apparentlyiodine-deficient , estradiol-treated ratsshowed cystic changes, periductal fibro-sis, lobular hyperplasia, and other symp-toms similar to those seen in benignbreast disease. These pathologic changes,associated with a higher breast-cancerrisk in women, were reversed wheniodine was reintroduced into the rat diet,leading investigators to conclude thatiodine deficiency enhances mammary-tis-sue sensitivity to estrogen.

Progestins appear to enhance iodine-related suppression of breast cancer pro-liferation in rats, and there is an ongoingstudy of patients with metastatic breastdisease, combining iodine supplementa-tion and a progest in.3 Further work isrequired to understand the relationship

between iodine and natural progesteroneor synthetic progestins better.

Iodine supplementation apparently sig-nificantly reduced mastalgia in a Russianstudy and significantly reduced the preva-lence of breast cysts , fibrous- t i ssueplaques, and breast pain in another,according to one review. One uncon-trolled clinical trial found that 3–6 mg ofaqueous iodine could reduce symptomsand reduce or eliminate fibrosis in womenwith fibrocystic breast changes.4 Epidemi-ologic analysis has apparently establisheda signif icant correlation between lowiodine intake and higher breast-cancermortality in various regions of Spain.Another epidemiologic analysis foundthat low iodine intake correlated to a high-er incidence of breast, endometrial, andovarian cancers.5 The author of that studyhypothesized that low iodine may haveinduced higher levels of gonadotropins(luteinizing hormone and follicle-stimulat-ing hormone) and thus created a highestrogen state with estradiol and estronedominance over estriol.

One reviewer pointed out that breast-cancer mortality was not affected by thereduction in endemic goiter in the UnitedStates after the introduction of iodizedsalt and suggested that components ofseaweed other than iodine may be thereal benefactor in reducing breast cancer.

There are only a few studies on varioussea vegetables and breast cancer, but theexisting studies show that seaweeds canexert antitumor effects in breast cancer.Several seaweed species inhibited tumori-genesis in a comparative study of seaweedsin rats.6 Six different seaweeds (fourkombu species, a nori species, and Eiseniabicyclis) fed as 2 percent of the diet wereevaluated for their effect on 7,12-dimethyl-

32

Herbs and Breast Cancer Research Review of Seaweed, Rosemary, and Ginseng

benz[a]anthracene (DMBA)–induced mam-mary tumorigenesis in rats. Nori and thekombu species Laminaria religiosa (LR) andL. japonica (LJ) had a strong inhibitory effecton tumor initiation. The incidence of cancerwas 35 percent for rats who were fed noriand LR and 50 percent for rats who werefed LJ compared to 67 percent in the con-trol group. Nori and LR also significantlydelayed the time to the development of afirst-palpable tumor compared to controls.Rats who were fed LR had a much lowertumor weight (1.6 g compared to 16.3 g incontrols). None of the rats who were fednori or LR died of DMBA toxicity. Theauthors concluded that seaweeds appear tohave two beneficial actions in animal mod-els of breast cancer: (1) immunopotentia-tion that enhances the host’s defensemechanism against neoplasia and (2) ananticarcinogenic activity that is probablyrelated to seaweed’s dietary fiber content.

Wakame signi f icantly suppressedDMBA-induced tumor growth in rats inanother study and the tumors that devel-oped were significantly smaller than incontrols.7 Rats who were fed wakame hadh i ghe r b lo od l ev e l s o f i od in e andimmunohistochemical studies suggestedthat iodine was transported from theb lood to th e mammary t issue s andinduced apoptosis via the expression oftransforming growth factor- b . Anotherstudy that attempted to determine whichconstituent was responsible for seaweed’santitumor activity found that the ethanolextract of kombu (Laminaria angustata)had a potent, dose-dependent effect onDMBA and 3 ,2 ’ -d imethyl -4 -am ino-biphenyl (both breast carcinogens) in theAmes/Mammalian Microsome assay in96 percent of the strains that were testedin the study.8 The hot- and cold-water

extracts showed dose-dependent, moder-ate activity in vitro. Kombu, as 5 percentof the diet, signif icantly delayed theappearance of tumors (19 weeks in treat-ed rats versus 11 weeks in controls),reduced the number of tumors per rat,and reduced the number of adenocarcino-mas (63 percent versus 76 percent in con-trols) in rats administered DMBA.9

Most early and some late-stage breastcancers are estrogen-sensitive. It is there-fore logical to encourage patients withbreast cancer to include seaweed in theirdiets because iodine deficiency may makemammary tissue more estrogen sensitiveand noniodine compounds in seaweedmay have other antitumor effects andmay enhance the movement of iodinefrom the blood to the mammary tissue.

Seaweed also appears to reduce theabsorp tion o f carc inogens from theintestines. The synergistic effect of estro-genic pesticide residues in the diet andair are of increasing concern in estrogen-sensi tive breast-cancer induction andpromotion .10 Prel iminary scient i f icresearch shows that seaweed may reducethe effect of xenoestrogens and other car-cinogens in the diet. However, there arereports that an excessive intake of dietaryiodine has been correlated with a higherincidence of thyroid cancer.11 A reason-able compromise may be to recommendthat patients add more nori to their diets.Nori has strong antimutagenic activity inthe studies but contains less iodine thanother seaweeds. Nori is also reported tobe an excellent source of vitamin B12 andmay be a v a lu ab l e supp l emen t f orwomen who adopt a stricter vegetariandiet in order to reduce the negative effectof animal fats on breast cancer. Unfortu-nately, some clinical trial data suggest

that the form of vitamin B12 in sea veg-etables may be absorbed but is not able tobe utilized by cells.12 Further investiga-tion is warranted.

Rosemary

In Western botanical medicine, rose-mary is used mainly for the treatment ofconstitutional hypotension and circulato-ry disorders, to heal and protect skin,and to enhance memory funct ion inelderly patients. Rosemary was usedgenerical ly as a cancer trea tment inmany traditions and was specificallyused for liver but not for breast cancer inChile.13 Nonetheless, rosemary showssome exciting potential in treating breastcancer. First, as part of the diet, rosemary

ALTERNATIVE & COMPLEMENTARY THERAPIES—FEBRUARY 2001 33

A reasonable compromise may be to recommend that

patients add more nori to their diets.

Laminaria japonica. Drawing by Kathy Abas-cal, B.S., J.D.

inhibits tumor formation in rats. Second,rosemary had a significant effect on theaccumulation of chemotherapy agents inmultidrug-resistant breast-cancer cells invitro. Third, rosemary extract that hasbeen administered orally has shownantitumor effects that its isolated con-stituents lack.

Rats who were fed rosemary as 1 per-cent of their diets developed 47 percentfewer DMBA-induced cancers comparedto control rats. And when the rats werefed rosemary as 0.5 and 1 percent oftheir diets, the rats showed 42 percentless binding of DMBA to breast epithe-l ia l- ce ll DNA.14 The rosemary con-s t i tuents carnoso l and urso l ic ac idadded as 0.5 percent of the rats’ dietsdid not inhibi t in vivo DMBA-DNAadducts, while 0.5 percent of rosemaryin the rats’ diets inhibited DNA adductformation significantly. When injectedint raper i tonea l ly (200 mg/kg for 5days), carnosol inhibited 40 percent ofadducts compared to controls; rosemaryinhibited 44 percent, and ursolic acidwas ineffective in this same assay.15

In a meet ing abst rac t , S ingl e taryreported that rosemary’s effect on breastcancer showed inhibitory effects beyondthe initiation stage: Dietary rosemaryreduced tumor incidence and tumorweight in rats who were maintained onrosemary throughout the study. Butwhen rosemary was administered for ashorter period after DMBA administra-tion, tumor incidence was significantlyreduced init ially but terminal tumori n c i d e n c e w a s s i m i l a r t o t h a t o fcontrols.16 Another researcher, however,reported that dietary rosemary inhibitedDMBA-tumor initiation but had littleeffect when administered after the initia-tion period.17 It also appears that rose-

mary’s antitumor effect may be affectedby the types and amounts of lipids inthe diet. Rosemary had a much strongereffect on rats who were fed a 20-percentcorn-oil diet than the herb had on ratswho were fed a 5-percent corn-oil and a15 percent coconut-oil diet. At both 0.5and 1 percent of the rats’ diets, rosemaryinhibited DMBA-induced mammary-tumor formation significantly in ratswho were fed a corn-oil diet but in the5/15 diet , the lower dose of rosemarywas ineffective.18

Many mammary cells become resistantto chemotherapy agents because of a P-glycoprotein pump that transports thedrugs out of the cancer cells. Rosemarywas incubated with drug-sensitive, wildtype, and R65 MCF-7 doxorubicin (Adri-amycin)–resistant human breast-cancercells.19 Rosemary had no effect on thedoxorubicin accumulation in the wildtype cells but decreased the efflux of dox-orubicin from the drug-resistant cells by31 percent . A second in vi t ro studyshowed that rosemary extract increasedthe intracellular concentration of doxoru-bicin and vinblastine in a line of drug-resistant human breast-cancer cells andalso appeared to increase their sensitivityto these agents.20

Rosemary is bioavailable when it isappl ied top ical ly , and prel iminaryresearch shows that it inhibits tumor initi-ation and promotion in mouse skin.21

Historically, rosemary baths were pre-scribed to strengthen the nervous and cir-culatory systems22 and wine decoctionsof rosemary were dispensed to increaseappetite in patients.23 Thus, it may makesense to revive traditional practices ofadministering rosemary both topicallyand internally to women with breast-can-cer concerns.

American Ginseng

American ginseng is used as an adapto-gen to increase both physical and mentalendurance and is believed to act on thenonspecific stress response and to nor-malize counterproductive hypothalamicactivity. American ginseng is typicallyused as a strengthening and calming tonicin middle-age patients who are beingworn down physically and/or mentally.In the Traditional Chinese Medicineframework, this is considered to workwell for persons with excess heat and is acommon ingredien t in menopausal for-mulas. In contrast, Asian ginseng (Panaxginseng) is used as a tonic for patientswho are elderly, weak, and feeble. Ameri-can ginseng is almost always given forextended periods of time and is not usedfor its short-term effects.

American ginseng has a paradoxicaleffect on estrogen-sensitive breast-cancerlines in vitro. While American ginsenginduces the expression of an estrogen-reg-ulated gene, it does not increase the pro-liferative phase of the cell cycle.24 Theexpression of pS2, an estrogen-regulatedgene, was tested in three breast-cancercell lines (MCF-7, T-47D, and BT-20) byblot analysis, and competitive studieswere performed with estradiol, Americanginseng, and tamoxifen. Both Americanginseng and estradiol induced the expres-sion of pS2 RNA and protein in MCF-7cells while tamoxifen suppressed pS2expression. None of the agents increasedexpression in T-47D or BT-20 cell lines.Estradiol had a proliferative effect on thecells and tamoxifen had an inhibitoryeffect, while American ginseng did nothave a significant effect on cell prolifera-tion. The researchers concluded thatAmerican ginseng would have a protec-

34 ALTERNATIVE & COMPLEMENTARY THERAPIES—FEBRUARY 2001

Rosemary’s antitumor effect may be affected by the types and amounts of lipids in the diet.

tive effect against breast cancer althoughthe herb’s effect may, in part, be mediatedby the estrogen receptor.

In a subsequent in vitro experiment ,American ginseng was shown to cause asignificant, dose-dependent decrease incell proliferation compared to controlswhile estradiol increased the proliferativephase and decreased the resting phase ofthe cell cycle.25 American ginseng wasfound to suppress cell growth significant-ly and synergistically when combinedwith chemotherapy agents. American gin-seng increased the growth inhibitoryeffect of tamoxifen, cyclophosphamide,f luorouracil, doxorubicin, paclitaxel(Taxol), methotrexate, and megestrolcompared to their effects alone (P<0.005).Two of these agents (cyclophosphamideand fluorouracil) actually did not have asignificant growth inhibitory effect alonebut inhibited growth when combinedwith American ginseng in vitro. Theresearchers concluded that American gin-seng is likely to augment chemotherapyfor breast cancer and might be a veryi mp o r t a n t a g e n t f o r c o n t r o l l i n gmenopausal symptoms in women whoare on prolonged tamoxifen or megestrol(Megace) therapy.

These researchers also reported on theestrogenicity of American ginseng com-pared to Asian ginseng grown in Chinaand Korea.26 All three ginsengs increasedpS2 RNA expression in a dose-dependentfashion and also increased progesterone-receptor expression. However, AmericanGinseng and Asian ginseng grown inChina did not stimulate MCF-7 cell growthwhile Korean-grown Asian ginsengincreased proliferation 150 percent. Otherresearch shows that the use of ginsengproducts requires some caution becausemany ginseng products contain little or no

ginseng and often misrepresent the type ofginseng present.27 Moreover, the geo-graphic location and manner in whichAmerican ginseng is cultivated affects itsmedicinal properties: Studies have shownthat wild harvested American ginsengappears to be of better quality than Ameri-can cultivated ginseng, and that Americancultivated ginseng appears to be of betterquality than Chinese cultivated ginseng.28

Fortunately, many high-quality woods cul-tivated and organically grown Americanginseng products are available.

There are no known human clinical tri-als examining the effect of American gin-seng on women with breast cancer. Therehave been several epidemiologic studiesshowing that Asian ginseng intake in thediet in Korea is associated with dramati-cally lower overall cancer rates.29 Howev-er, although overall cancer mortality waslower in women who consumed Asianginseng regularly compared to those whodid not, breast cancer rates specificallywere not affected.30 A prospective clinicaltrial of Asian and American ginseng iswarranted to determine what effects itwould have in preventing cancers of alltypes, including breast cancer.

Summary

Definitive clinical trials of sustainablesources of the three plants reviewed inthis article are needed to determine theirimpact on women with breast cancer.Nevertheless , each of the three plantsreviewed in this article show some poten-tial benefit in treating breast cancer. Noneis the cure for cancer but each appears todelay and inhibit tumor formation. Twoof the plants, rosemary and Americanginseng, also show a potential ability toenhance the effectiveness of conventional

chemotherapy treatment of breast cancer.Patients can be encouraged to make sea-weed a pleasant, tasty addition to theirdiets. Rosemary is a popular cooking herbwith a long his to ry o f use in herba lmedicine. American ginseng is a tonicstrengthener that is reported to help alle-viate menopausal symptoms. None ofthese plants show toxicity at usual doses,and research indicates that we may bene-fit our patients by giving these herbs agreater role in our treatment of womenwith breast cancer or women who are athigh risk of developing breast cancer. n

References1. Teas, J. The consumption of seaweed as aprotective factor in the etiology of breast can-cer. Med Hypotheses 7(5):610–613, 1981.

ALTERNATIVE & COMPLEMENTARY THERAPIES—FEBRUARY 2001 35

Researchers concluded that American ginseng is likely to augment chemotherapy for breast cancer.

Rosmarinus officinalis.

2. Cann, S.A., van Netten, J.P., van Netten, C.Hypothesis: Iodine, selenium and the develop-ment of breast cancer. Cancer Cause Control11:121–127, 2000.3. Cann, S.A., van Netten, C., van Netten, J.P.Implementation of a study combining pro-gestin treatment with iodine and seleniumsupplements in advanced breast cancer [abstr.#C-57]. AACR/JCA Fourth Joint Conference,1998.4. Ghent, W.R., Eskin, B.A. Elemental iodinesupplementation in clinical breast dysplasia[abstr.]. Proc Ann Meeting Am Assoc Cancer Res27:189, 1986.5. Stadel , V.V. Dietary iodine and risk ofbreast, endometrial, and ovarian cancer. Lanceti:890–891, 1976.6. Yamamoto, I., Maruyama, H., Moriguchi, M.The effect of dieta ry seaweeds on 7,12-di-methyl-benz[a]anthracene-induced mammarytumorigenesis in rats. Cancer Lett 35(2):109–118,1987.7. Funahashi, H., Imai, T., Tanaka, Y., et al.Wakame seaweed suppresses the proliferationof 7, 12-dimethylbenz[a]anthracene-inducedtumors in rats. Jpn J Cancer Res 90(9):922–927,1999.8. Reddy, B.S., Sharma, C., Mathews, L. Effectof Japanese seaweed (Laminaria angustata)extracts on the mutagenicity of 7,12-dimethyl-benz[a]anthracene, a breast carcinogen, and of3,2’-dimethyl-4-aminobiphenyl, a colon andbreast carcinogen. Mutat Res 127(2):113–118,1984.9. Teas, J., Harbison, M.L., Gelman, R.S. Dietaryseaweed (Laminaria) and mammary carcinogen-esis in rats. Cancer Res 44(7):2758–2761, 1984.10. Verma, S.P., Salamone, E., Goldin, B. Cur-cumin and genistein, plant natural productsshow synergist ic inhibitory effects on thegrowth of human breast cancer MCF-7 cellsinduced by estrogenic pesticides. Biochem Bio-phys Res Comm 233:692–696, 1997.11. Kim, J.Y., Kim, K.R. Dietary iodine intakeand urinary iodine excretion in patients withthyroid diseases. Yonsei Med J 41(1):22–28,2000.12. Dagnelie, P.C., van Staverene, W.A., van

den Verg, H. Vitamin B-12 from algae appearsno t to be b io a va i l ab l e . Am J C l i n Nut r53:695–697, 1991.13. Hartwell, J.L. Plants Used Against Cancer.Lawrence, MA: Quarterman Publications,1982, pp. 271–272.14. Singletary, K.W., Nelshoppen, J.M. Inhibi-t ion of 7,12-dimethylbenz[a]anthracene(DMBA)-induced mammary tumorigenesisand of in vivo formation of mammary DMBA-DNA adducts by rosemary extract. Cancer Lett60(2):169–175, 1991.15. Singletary, K., MacDonald, C., Wallig, M.Inhibition by rosemary and carnosol of 7,12-dimethylbenz[a]anthracene (DMBA)–inducedrat mammary tumorigenes is and in vivoDMBA-DNA adduct formation. Cancer Lett104(1):43–48, 1996.16. Singletary, K. Inhibition of DMBA-inducedmammary tumorigenesis by rosemary extract(meeting abstr.). FASEB J 5(5):A927, 1991.17. Huang, M.T. , Ma, W. , Ho, C.T. , et al .Inhibitory effect of dietary rosemary on mam-mary and colon carcinogenesis in mice (meet-ing abstr.). Proc Annu Meet Am Assoc CancerRes 36:A3514, 1995.18. Amagase, H., Sakamoto, K., Segal, E.R., eta l . D i e t a ry r o semary supp r es s es 7 , 12 -dimethylbenz(a)anthracene binding to ratmammary cell DNA. J Nutr 126(5):1475–1480,1996.19. Plouzek, C.A., Daschner, P., Lopaczynska,J, et al. Rosemary extract inhibits P-glycopro-tein mediated drug efflux in multidrug resis-tant MCF-7 cells (meeting abstr.). Proc AnnuMeet Am Assoc Cancer Res 37:A2263, 1996.20. Plouzek, C.A., Ciolino, H.P., Clarke, R., et al.Inhibition of P-glycoprotein activity and rever-s a l o f mu l t id rug r es i s tan ce in v i t ro by rosemary extract. Eur J Cancer 35(10):1541–1545,1999.21. Huang, M.T., Ho, C.T., Wang, Z.Y., et al.Inhibition of skin tumorigenesis by rosemaryand its constituents carnosol and ursolic acid.Cancer Res 54(3):701–708, 1994.22. Weiss, R.F., Fintelmann, V. Herbal Medicine.(2nd ed., rev. & exp.) New York: Thieme, 1988,p. 176.

23. Grieve, M.M. A Modern Herbal. New York:Dorset Press, 1994, pp. 681–683.24. Duda, R.B., Taback, B., Kessel, B., et al. pS2Expression induced by American ginseng inMCF-7 breast cancer cells . Ann Surg Oncol3(6):515–520, 1996.25. Duda, R.B., Zhong, Y., Navas, V., et al.American ginseng and breast cancer therapeu-tic agents synergistically inhibit MCF-7 breastcancer cell growth. J Surg Oncol 72(4):230–239,1999.26. Duda, R.B., Taback ,B., Navas, V., et al.Comparison of estrogenicity of Panax quinque-folium and Panax CA Meyer in MCF-7 breastcancer cells (meeting abstr.). Proc Annu MeetAm Assoc Cancer Res 38:A756, 1997.27. Liberti, L.E., Der Marderosian, A. Evalua-tion of commercial ginseng products. J PharmSci 67(10):1487–1489, 1978.28. Chuang, W., Wuk, H., Sheu, S., et al. Acomparative study on commercial samples ofGinseng radix. Planta Med 61:459–465, 1995.29. Yarnell, E. Prevention of cancer with botan-ical medicines [review]. ALTERNATIVE &COMPLEMENTARY THERAPIES 3(6):427–4321997.30. Yun, T.K., Choi, S.Y. Preventive effect ofginseng intake against various human cancers:A case-control study on 1987 pairs. Cancer Epi-dem Biomarkers Prevention 4:401–408, 1995.

Kathy Abascal, B.S., J.D., is a certified herbal-ist and is executive director of the BotanicalMedicine Academy, Vashon, Washington. EricYarnell, N.D., is chair of the department of thebotanical medicine department at SouthwestCollege of Naturopathic Medicine, Tempe, Ari-zona. He is president of the Botanical MedicineAcademy, a specialty board for using medici-nal herbs.

To order reprints of this article, write to or call:Karen Ballen, ALTERNATIVE & COMPLE-MENTARY THERAPIES, Mary Ann Liebert,Inc., 2 Madison Avenue, Larchmont, NY 10538-1962, (914) 834-3100.

36 ALTERNATIVE & COMPLEMENTARY THERAPIES—FEBRUARY 2001