Summary
Background
People diagnosed with cancer often self-administer complementary and alternative medicines (CAMs) to supplement their conventional treatments, improve health, or prevent recurrence. Flor-Essence® and Essiac® Herbal Tonics are commercially available complex mixtures of herbal extracts sold as dietary supplements and used by cancer patients based on anecdotal evidence that they can treat or prevent disease. In this study, we evaluated Flor-Essence® and Essiac® for their effects on the growth of human tumor cells in culture.
Methods
The effect of Flor-Essence® and Essiac® herbal tonics on cell proliferation was tested in MCF-7, MDA-MB-436, MDA-MB-231, and T47D cancer cells isolated from human breast tumors. Estrogen receptor (ER) dependent activation of a luciferase reporter construct was tested in MCF-7 cells. Specific binding to the ER was tested using an ICI 182,780 competition assay.
Results
Flor-Essence® and Essiac® herbal tonics at 1%, 2%, 4% and 8% stimulated cell proliferation relative to untreated controls in both estrogen receptor positive (MCF-7 and T47D) and estrogen receptor negative (MDA-MB-231 and MDA-MB-436) cell lines. Exposure to the tonics also produced a dose-dependent increase in ER dependent luciferase activity in MCF-7 cells. A 10−7 M concentration of ICI 182,780 inhibited the induction of ER dependent luciferase activity by Flor-Essence® and Essiac®, but did not affect cell proliferation.
Conclusion
Flor-Essence® and Essiac® Herbal Tonics can stimulate the growth of human breast cancer cells through ER mediated as well as ER independent mechanisms of action.
Similar content being viewed by others
References
Ernst E, 2001 Complementary and alternative medicine Lancet 357(9258):802–803
Ernst E, 2001 Alternative cancer cures Br J Cancer 85(5):781–782
Kaegi E, 1998 Unconventional therapies for cancer: 1. Essaic CMAJ 158:897–902
Smith M, Boon H, 1999 Counseling cancer patients about herbal medicine Patient Education and Counseling 38:109–120
Ernst E, Cassileth B, 1999 How useful are unconventional cancer treatments? Eur J Cancer 35:1608–1613
Boutin PD, Buchwald D, Robinson L, Collier AC, 2000 Use of and attitudes about alternative and complementary therapies among outpatients and physicians at a municipal hospital J Altern Complement Med 6(4):335–343
Richardson M, Sanders T, Tamayo C, Perez C, Palmer J, 2000 Flor-Essence® herbal tonic use in North America: A profile of general consumers and cancer patients Herbalgram 50:40–46
De Smet PA, 2002 Herbal remedies N Engl J Med 347(25):2046–2056
Marcus DM, Grollman AP, 2002 Botanical medicines–the need for new regulations N Engl J Med 347(25):2073–2076
Penson RT, Castro CM, Seiden MV, Chabner BA, Lynch TJ Jr., 2001 Complementary, alternative, integrative, or unconventional medicine? Oncologist 6(5):463–473
Werneke U, Earl J, Seydel C, Horn O, Crichton P, Fannon D, 2004 Potential health risks of complementary alternative medicines in cancer patients. Br J Cancer 90(2):408–413
http://www.mdanderson.org
Percival J, 1994 The Essiac Handbook2ndRideout Publishing CompanyOrlando, FL
Stainsby M: Kee** hope alive. In: The Vancouver Sun. Vancouver, 1992
Mills E, Ernst E, Singh R, Ross C, Wilson K, 2003 Health food store recommendations: implications for breast cancer patients Breast Cancer Res 5(6):R170–174
Whitaker J: Should you take Essiac tea against cancer? In: Dr Whitaker’s Newsletter. Vol. 5, 1995 http://www.drwhitaker.com/
Straus SE, 2002 Herbal medicines–what’s in the bottle? N Engl J Med 347(25):1997–1998
Tamayo C, Richardson M, Diamond S, Skoda I, 2000 The chemistry and biological activity of herbs used in Flor-Essence™ Herbal Tonic and Essiac™ Phytother Res 14:1–14
Burdette JE, Liu J, Lantvit D, Lim E, Booth N, Bhat KP, Hedayat S, Van Breemen RB, Constantinou AI, Pezzuto JM, et al. 2002 Trifolium pratense (Red Clover) Exhibits Estrogenic Effects In Vivo in Ovariectomized Sprague-Dawley Rats J Nutr 132(1):27–30
Bucher JR, Lucier G, 1998 Current approaches toward chemical mixture studies at the National Institute of Environmental Health Sciences and the U.S National Toxicology Program Environ Health Perspect 106Suppl6:1295–1298
Hansen H, De Rosa CT, Pohl H, Fay M, Mumtaz MM, 1998 Public health challenges posed by chemical mixtures Environ Health Perspect 106(Suppl 6):1271–1280
Yang RS, 1998 Some critical issues and concerns related to research advances on toxicology of chemical mixtures Environ Health Perspect 106(Suppl 4):1059–1063
Connor K, Ramamoorthy K, Moore M, Mustain M, Chen I, Safe S, Zacharewski T, Gillesby B, Joyeux A, Balaguer P, 1997 Hydroxylated polychlorinated biphenyls (PCBs) as estrogens and antiestrogens: structure-activity relationships Toxicol Appl Pharmacol 145(1):111–123
Gaido K, Dohme L, Wang F, Chen I, Blankvoort B, Ramamoorthy K, Safe S, 1998 Comparative estrogenic activity of wine extracts and organochlorine pesticide residues in food Environ Health Perspecti 106(Suppl 6):1347–1351
McLachlan JA, 1993 Functional toxicology: a new approach to detect biologically active xenobiotics Environ Health Perspect 101(5):386–387
Payne J, Scholze M, Kortenkamp A, 2001 Mixtures of four organochlorines enhance human breast cancer cell proliferation Environ Health Perspect 109(4):391–397
Shelby MD, Newbold RR, Tully DB, Chae K, Davis VL, 1996 Assessing environmental chemicals for estrogenicity using a combination of in vitro and in vivo assays Environ Health Perspect 104(12):1296–1300
Soto AM, Chung KL, Sonnenschein C, 1994 The pesticides endosulfan, toxaphene, and dieldrin have estrogenic effects on human estrogen-sensitive cells Environ Health Perspect 102(4):380–383
Soto AM, Sonnenschein C, Chung KL, Fernandez MF, Olea N, Serrano FO, 1995 The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants Environ Health Perspect 103(Suppl 7):113–122
Zacharewski T, 1998 Identification and assessment of endocrine disruptors: limitations of in vivo and in vitro assays Environ Health Perspect 106(Suppl 2):577–582
Klotz DM, Beckman BS, Hill SM, McLachlan JA, Walters MR, Arnold SF, 1996 Identification of environmental chemicals with estrogenic activity using a combination of in vitro assays Environ Health Perspect 104(10):1084–1089
Reel JR, Lamb IJ, Neal BH, 1996 Survey and assessment of mammalian estrogen biological assays for hazard characterization Fundam Appl Toxicol 34(2):288–305
Safe S, Connor K, Gaido K, 1998 Methods for xenoestrogen testing Toxicol Lett 102–103:665–670
Nodland KI, Wormke M, Safe S, 1997 Inhibition of estrogen-induced activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the MCF-7 human breast cancer and other cell lines transfected with vitellogenin A2 gene promoter constructs Arch Biochem Biophys 338:67–72
Charles GD, Gennings C, Clemons J, Zacharewski TR, Gollapudi BB, Carney EW, 2000 Optimization of an estrogen receptor-alpha transcriptional activation assay for testing a diverse spectrum of chemicals J Appl Toxicol 20(6):449–454
Rogers JM, Denison MS, 2000 Recombinant cell bioassays for endocrine disruptors: development of a stably transfected human ovarian cell line for the detection of estrogenic and anti-estrogenic chemicals In Vitr Mol Toxicol 13(1):67–82
Ihaka R, Gentleman R, 1996 A language for data analysis and graphics J Comut Graph Stat 5:299–314
Pinheiro JC, Bates DM, 2000 Mixed-effects Models in S and S-PLUS Springer-Verlag New York
Benjamini Y, Hochberg Y, 1995 Controlling the false discovery rate: a practical and powerful approach to multiple testing J Royal Stat Soc Ser B (Methodological) 57:289–300
DeFriend DJ, Anderson E, Bell J, Wilks DP, West CM, Mansel RE, Howell A, 1994 Effects of 4-hydroxytamoxifen and a novel pure antioestrogen (ICI 182780) on the clonogenic growth of human breast cancer cells in vitro Br J Cancer 70(2):204–211
Howell A, DeFriend D, Robertson J, Blamey R, Walton P, 1995 Response to a specific antioestrogen (ICI 182780) in tamoxifen-resistant breast cancer Lancet 345(8941):29–30
Rasmussen TH, Nielsen JB, 2002 Critical parameters in the MCF-7 cell proliferation bioassay (E-Screen) Biomarkers 7(4):322–336
Hayashi S, Sakamoto T, Inoue A, Yoshida N, Omoto Y, Yamaguchi Y, 2003 Estrogen and growth factor signaling pathway: basic approaches for clinical application J Steroid Biochem Mol Biol 86(3–5):433–442
Campbell RA, Bhat-Nakshatri P, Patel NM, Constantinidou D, Ali S, Nakshatri H, 2001 Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance J Biol Chem 276(13):9817–9824
Feng W, Webb P, Nguyen P, Liu X, Li J, Karin M, Kushner PJ, 2001 Potentiation of estrogen receptor activation function 1 (AF-1) by Src/JNK through a serine 118-independent pathway Mol Endocrinol 15(1):32–45
Smith CL, 1998 Cross-talk between peptide growth factor and estrogen receptor signaling pathways Biol Reprod 58(3):627–632
Beck V, Rohr U, Jungbauer A, 2005 Phytoestrogens derived from red clover: an alternative to estrogen replacement therapy? J Steroid Biochem Mol Biol 94(5):499–518
Fritz WA, Coward L, Wang J, Lamartiniere CA, 1998 Dietary genistein: perinatal mammary cancer prevention, bioavailability and toxicity testing in the rat Carcinogenesis 19(12):2151–2158
Cotroneo MS, Wang J, Fritz WA, Eltoum IE, Lamartiniere CA, 2002 Genistein action in the prepubertal mammary gland in a chemoprevention model Carcinogenesis 23(9):1467–1474
Lamartiniere CA: Protection against breast cancer with genistein: a component of soy. Am J Clin Nutr. 71(6 Suppl): 1705S-1707S, 2000 (discussion 1708S-1709S)
Lamartiniere CA, Cotroneo MS, Fritz WA, Wang J, Mentor-Marcel R, Elgavish A, 2002 Genistein chemoprevention: timing and mechanisms of action in murine mammary and prostate J Nutr 132(3):552S–558S
Constantinou AI, Krygier AE, Mehta RR, 1998 Genistein induces maturation of cultured human breast cancer cells and prevents tumor growth in nude mice Am J Clin Nutr 68(6 Suppl):1426S–1430S
Hilakivi-Clarke L, Cho E, Clarke R, 1998 Maternal genistein exposure mimics the effects of estrogen on mammary gland development in female mouse offspring Oncol Rep 5(3):609–616
Hilakivi-Clarke L, Cho E, Onojafe I, Raygada M, Clarke R, 1999 Maternal exposure to genistein during pregnancy increases carcinogen-induced mammary tumorigenesis in female rat offspring Oncol Reports 6:1089–1095
Chen WF, Huang MH, Tzang CH, Yang M, Wong MS, 2003 Inhibitory actions of genistein in human breast cancer (MCF-7) cells Biochim Biophys Acta 1638(2):187–196
Ottenweller J, Putt K, Blumenthal EJ, Dhawale S, Dhawale SW, 2004 Inhibition of prostate cancer-cell proliferation by Essiac J Altern Complement Med 10(4):687–691
Tai J, Cheung S, Wong S, Lowe C, 2004 In vitro comparison of Essiac and Flor-Essence on human tumor cell lines Oncol Rep 11(2):471–476
Yap SP, Shen P, Butler MS, Gong Y, Loy CJ, Yong EL, 2005 New estrogenic prenylflavone from Epimedium brevicornum inhibits the growth of breast cancer cells Planta Med 71(2):114–119
Ravindranath MH, Muthugounder S, Presser N, Viswanathan S, 2004 Anticancer therapeutic potential of soy isoflavone, genistein Adv Exp Med Biol 546:121–165
Bennett LM, Montgomery JL, Steinberg SM, Kulp KS, 2004 Flor-Essence herbal tonic does not inhibit mammary tumor development in Sprague Dawley rats Breast Cancer Res Treat 88(1):87–93
Schmidt K, Ernst E, 2004 Assessing websites on complementary and alternative medicine for cancer Ann Oncol 15(5):733–742
Matthews SC, Camacho A, Mills PJ, Dimsdale JE, 2003 The internet for medical information about cancer: help or hindrance? Psychosomatics 44(2):100–103
Malik IA, Gopalan S, 2003 Use of CAM results in delay in seeking medical advice for breast cancer Eur J Epidemiol 18(8):817–822
Eysenbach G, 2003 The impact of the Internet on cancer outcomes CA Cancer J Clin 53(6):356–371
Acknowledgements
We thank Mark Knize for technical assistance with the HPLC analysis of the tonics. This publication was made possible, in part, by grant number 7IB-0003 from the California Breast Cancer Research Program, grant number R21AT001730-02 from the National Center for Complementary and Alternative Medicine (NCAM) and grant number K22 ES00322–01 from the National Institute of Environmental Health Sciences (NIEHS), NIH. It’s contents are solely the responsibility of the authors and do not necessarily represent the official view of the NCAM, NIEHS, NIH or LLNL. This work was performed under the auspices of the U.S. Department of Energy by the University of California, Lawrence Livermore National Laboratory under contract No. W-7405-Eng-48.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kulp, K.S., Montgomery, J.L., Nelson, D.O. et al. Essiac® and Flor-Essence® herbal tonics stimulate the in vitro growth of human breast cancer cells. Breast Cancer Res Treat 98, 249–259 (2006). https://doi.org/10.1007/s10549-005-9156-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-005-9156-x