Planta Med 2010; 76(11): 1087-1093
DOI: 10.1055/s-0030-1250169
Cancer Therapy
Reviews
© Georg Thieme Verlag KG Stuttgart · New York

Natural Compounds with Aromatase Inhibitory Activity: An Update

Marcy J. Balunas1 , 2 , 3 , 4 , A. Douglas Kinghorn5
  • 1Division of Medicinal Chemistry, Department of Pharmaceutical Sciences, School of Pharmacy, Storrs, CT, USA
  • 2Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA, USA
  • 3Instituto de Investigaciones Científicas y Servicios de Alta Tecnología, Clayton, Panamá
  • 4Smithsonian Tropical Research Institute, Ancón, Panamá
  • 5Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH, USA
Further Information

Publication History

received February 3, 2010 revised May 28, 2010

accepted July 2, 2010

Publication Date:
15 July 2010 (online)

Abstract

Several synthetic aromatase inhibitors are currently in clinical use for the treatment of postmenopausal women with hormone-receptor positive breast cancer. However, these treatments may lead to untoward side effects and so the search for new aromatase inhibitors continues, especially those for which the activity is promoter-specific, targeting the breast-specific promoters I.3 and II. Recently, numerous natural compounds have been found to inhibit aromatase in noncellular, cellular, and in vivo studies. These investigations, covering the last two years, as well as additional studies that have focused on the evaluation of natural compounds as promoter-specific aromatase inhibitors or as aromatase inducers, are described in this review.

References

  • 1 Parkin D M, Fernandez L M. Use of statistics to assess the global burden of breast cancer.  Breast J. 2006;  12 (Suppl. 1) S70-S80
  • 2 Igene H. Global health inequalities and breast cancer: an impending public health problem for developing countries.  Breast J. 2008;  14 428-434
  • 3 Chlebowski R, Cuzick J, Amakye D, Bauerfeind I, Buzdar A, Chia S, Cutuli B, Linforth R, Maass N, Noguchi S, Robidoux A, Verma S, Hadji P. Clinical perspectives on the utility of aromatase inhibitors for the adjuvant treatment of breast cancer.  Breast. 2009;  18 (Suppl. 2) S1-S11
  • 4 Gibson L, Lawrence D, Dawson C, Bliss J. Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women.  Cochrane Database Syst Rev. 2009;  CD003370
  • 5 Chlebowski R T, Anderson G L, Geller M, Col N. Coronary heart disease and stroke with aromatase inhibitor, tamoxifen, and menopausal hormone therapy use.  Clin Breast Cancer. 2006;  6 (Suppl. 2) S58-S64
  • 6 Goss P E, Qi S L, Hu H Q, Cheung A M. The effects of atamestane and toremifene alone and in combination compared with letrozole on bone, serum lipids and the uterus in an ovariectomized rat model.  Breast Cancer Res Treat. 2007;  103 293-302
  • 7 Balunas M J, Su B, Brueggemeier R W, Kinghorn A D. Natural products as aromatase inhibitors.  Anticancer Agents Med Chem. 2008;  8 646-682
  • 8 Zhao J, Dasmahapatra A K, Khan S I, Khan I A. Anti-aromatase activity of the constituents from damiana (Turnera diffusa).  J Ethnopharmacol. 2008;  120 387-393
  • 9 Ye L, Gho W M, Chan F L, Chen S, Leung L K. Dietary administration of the licorice flavonoid isoliquiritigenin deters the growth of MCF-7 cells overexpressing aromatase.  Int J Cancer. 2009;  124 1028-1036
  • 10 Wang Y, Man Gho W, Chan F L, Chen S, Leung L K. The red clover (Trifolium pratense) isoflavone biochanin A inhibits aromatase activity and expression.  Br J Nutr. 2008;  99 303-310
  • 11 Su S L, Duan J A, Tang Y P, Zhang X, Yu L, Jiang F R, Zhou W, Luo D, Ding A W. Isolation and biological activities of neomyrrhaol and other terpenes from the resin of Commiphora myrrha.  Planta Med. 2009;  75 351-355
  • 12 Balunas M J, Su B, Brueggemeier R W, Kinghorn A D. Xanthones from the botanical dietary supplement mangosteen (Garcinia mangostana) with aromatase inhibitory activity.  J Nat Prod. 2008;  71 1161-1166
  • 13 Yang N Y, Li K, Yang Y F, Li Y H. Aromatase inhibitory fatty acid derivatives from the pollen of Brassica campestris L. var. oleifera DC.  J Asian Nat Prod Res. 2009;  11 132-137
  • 14 Balunas M J, Su B, Riswan S, Fong H H S, Brueggemeier R W, Pezzuto J M, Kinghorn A D. Isolation and characterization of aromatase inhibitors from Brassaiopsis glomerulata (Araliaceae).  Phytochem Lett. 2009;  2 29-33
  • 15 Balunas M J, Su B, Landini S, Brueggemeier R W, Kinghorn A D. Interference by naturally occurring fatty acids in a noncellular enzyme-based aromatase bioassay.  J Nat Prod. 2006;  69 700-703
  • 16 Paoletta S, Steventon G B, Wildeboer D, Ehrman T M, Hylands P J, Barlow D J. Screening of herbal constituents for aromatase inhibitory activity.  Bioorg Med Chem. 2008;  16 8466-8470
  • 17 Endringer D C, Guimaraes K G, Kondratyuk T P, Pezzuto J M, Braga F C. Selective inhibition of aromatase by a dihydroisocoumarin from Xyris pterygoblephara.  J Nat Prod. 2008;  71 1082-1084
  • 18 Ito A, Shamon L A, Yu B, Mata-Greenwood E, Lee S K, van Breemen R B, Mehta R G, Farnsworth N R, Fong H H S, Pezzuto J M, Kinghorn A D. Antimutagenic constituents of Casimiroa edulis with potential cancer chemopreventive activity.  J Agric Food Chem. 1998;  46 3509-3516
  • 19 Maiti A, Reddy P V, Sturdy M, Marler L, Pegan S D, Mesecar A D, Pezzuto J M, Cushman M. Synthesis of casimiroin and optimization of its quinone reductase 2 and aromatase inhibitory activities.  J Med Chem. 2009;  52 1873-1884
  • 20 McNulty J, Nair J J, Bollareddy E, Keskar K, Thorat A, Crankshaw D J, Holloway A C, Khan G, Wright G D, Ejim L. Isolation of flavonoids from the heartwood and resin of Prunus avium and some preliminary biological investigations.  Phytochemistry. 2009;  70 2040-2046
  • 21 Chomcheon P, Wiyakrutta S, Sriubolmas N, Ngamrojanavanich N, Kengtong S, Mahidol C, Ruchirawat S, Kittakoop P. Aromatase inhibitory, radical scavenging, and antioxidant activities of depsidones and diaryl ethers from the endophytic fungus Corynespora cassiicola L36.  Phytochemistry. 2009;  70 407-413
  • 22 Antia B S, Pansanit A, Ekpa O D, Ekpe U J M, Chulabhorn, Kittakoop P. Alpha-glucosidase inhibitory, aromatase inhibitory, and antiplasmodial activities of a biflavonoid GB1 from Garcinia kola stem bark.  Planta Med. 2010;  76 276-277
  • 23 Pontius A, Krick A, Mesry R, Kehraus S, Foegen S E, Muller M, Klimo K, Gerhauser C, Konig G M. Monodictyochromes A and B, dimeric xanthone derivatives from the marine algicolous fungus Monodictys putredinis.  J Nat Prod. 2008;  71 1793-1799
  • 24 Liu J, He C, Zhou K, Wang J, Kang J X. Coptis extracts enhance the anticancer effect of estrogen receptor antagonists on human breast cancer cells.  Biochem Biophys Res Commun. 2009;  378 174-178
  • 25 Flemming J, Madarnas Y, Franek J A. Fulvestrant for systemic therapy of locally advanced or metastatic breast cancer in postmenopausal women: a systematic review.  Breast Cancer Res Treat. 2009;  115 255-268
  • 26 Qiao Y, Cao J, Xie L, Shi X. Cell growth inhibition and gene expression regulation by (−)-epigallocatechin-3-gallate in human cervical cancer cells.  Arch Pharm Res. 2009;  32 1309-1315
  • 27 Ye L, Chan M Y, Leung L K. The soy isoflavone genistein induces estrogen synthesis in an extragonadal pathway.  Mol Cell Endocrinol. 2009;  302 73-80
  • 28 Sassi-Messai S, Gibert Y, Bernard L, Nishio S, Ferri Lagneau K F, Molina J, Andersson-Lendahl M, Benoit G, Balaguer P, Laudet V. The phytoestrogen genistein affects zebrafish development through two different pathways.  PLoS One. 2009;  4 e4935
  • 29 Takeda S, Yamamoto I, Watanabe K. Modulation of Δ 9-tetrahydrocannabinol-induced MCF-7 breast cancer cell growth by cyclooxygenase and aromatase.  Toxicology. 2009;  259 25-32
  • 30 Kellis Jr J T, Vickery L E. Inhibition of human estrogen synthetase (aromatase) by flavones.  Science. 1984;  225 1032-1034
  • 31 Le Bail J C, Champavier Y, Chulia A J, Habrioux G. Effects of phytoestrogens on aromatase, 3β- and 17β-hydroxysteroid dehydrogenase activities and human breast cancer cells.  Life Sci. 2000;  66 1281-1291
  • 32 Le Bail J C, Pouget C, Fagnere C, Basly J P, Chulia A J, Habrioux G. Chalcones are potent inhibitors of aromatase and 17β-hydroxysteroid dehydrogenase activities.  Life Sci. 2001;  68 751-761
  • 33 Saarinen N, Joshi S C, Ahotupa M, Li X, Ammala J, Makela S, Santti R. No evidence for the in vivo activity of aromatase-inhibiting flavonoids.  J Steroid Biochem Mol Biol. 2001;  78 231-239
  • 34 Lee D, Bhat K P L, Fong H H S, Farnsworth N R, Pezzuto J M, Kinghorn A D. Aromatase inhibitors from Broussonetia papyrifera.  J Nat Prod. 2001;  64 1286-1293
  • 35 van Meeuwen J A, Nijmeijer S, Mutarapat T, Ruchirawat S, de Jong P C, Piersma A H, van den Berg M. Aromatase inhibition by synthetic lactones and flavonoids in human placental microsomes and breast fibroblasts – a comparative study.  Toxicol Appl Pharmacol. 2008;  228 269-273
  • 36 Monteiro R, Becker H, Azevedo I, Calhau C. Effect of hop (Humulus lupulus L.) flavonoids on aromatase (estrogen synthase) activity.  J Agric Food Chem. 2006;  54 2938-2943
  • 37 Monteiro R, Faria A, Azevedo I, Calhau C. Modulation of breast cancer cell survival by aromatase inhibiting hop (Humulus lupulus L.) flavonoids.  J Steroid Biochem Mol Biol. 2007;  105 124-130
  • 38 Sanderson J T, Hordijk J, Denison M S, Springsteel M F, Nantz M H, van den Berg M. Induction and inhibition of aromatase (CYP19) activity by natural and synthetic flavonoid compounds in H295R human adrenocortical carcinoma cells.  Toxicol Sci. 2004;  82 70-79
  • 39 Blanco J G, Gil R R, Bocco J L, Meragelman T L, Genti-Raimondi S, Flury A. Aromatase inhibition by an 11,13-dihydro derivative of a sesquiterpene lactone.  J Pharmacol Exp Ther. 2001;  297 1099-1105
  • 40 Kanamaru T, Nozaki Y M, Masayuki M. TAN-1085 and its aglycon as angiogenesis and aromatase inhibitors and their manufacture with Streptomyces species. Japanese Patent: JP02-289532. 1990
  • 41 Santen R J, Brodie H, Simpson E R, Siiteri P K, Brodie A. History of aromatase: saga of an important biological mediator and therapeutic target.  Endocr Rev. 2009;  30 343-375
  • 42 Bulun S E, Lin Z, Zhao H, Lu M, Amin S, Reierstad S, Chen D. Regulation of aromatase expression in breast cancer tissue.  Ann NY Acad Sci. 2009;  1155 121-131
  • 43 Ghosh D, Griswold J, Erman M, Pangborn W. X-ray structure of human aromatase reveals an androgen-specific active site.  J Steroid Biochem Mol Biol. 2010;  118 197-202
  • 44 Wong S T. Emerging treatment combinations: integrating therapy into clinical practice.  Am J Health Syst Pharm. 2009;  66 S9-S14

Dr. Marcy J. Balunas

Division of Medicinal Chemistry, Department of Pharmaceutical Sciences
School of Pharmacy

69 North Eagleville Road, Unit 3092

Storrs, CT 06269

USA

Phone: + 18 6 04 86 40 66

Fax: + 18 6 04 86 57 92

Email: marcy.balunas@uconn.edu