Natural Products as Aromatase Inhibitors

Abstract

With the clinical success of several synthetic aromatase inhibitors (AIs) in the treatment of postmenopausal estrogen receptor-positive breast cancer, researchers have also been investigating also the potential of natural products as AIs. Natural products from terrestrial and marine organisms provide a chemically diverse array of compounds not always available through current synthetic chemistry techniques. Natural products that have been used traditionally for nutritional or medicinal purposes (e.g., botanical dietary supplements) may also afford AIs with reduced side effects. A thorough review of the literature regarding natural product extracts and secondary metabolites of plant, microbial, and marine origin that have been shown to exhibit aromatase inhibitory activity is presented herein. Keywordsaromatase inhibitors; natural products; breast cancer; botanical dietary supplements BREAST CANCERWorldwide breast cancer estimates included over one million incident cases and almost 400,000 deaths in the year 2000 [1,2]. In the United States, over 178,000 women were expected to be diagnosed with breast cancer in 2007 with over 40,000 deaths occurring from the disease [3]. In developed countries, mortality from breast cancer has recently begun to decline, primarily due to earlier detection and improved treatments [4,5]. Breast cancer is thought to be a result of inherited genetic predisposition (e.g., mutations in genes such as BRCA-1, p53, PTEN/MMAC1, and/or ATM) and/or environmental factors (e.g., radiation exposure, dietary factors, alcohol consumption, hormonal exposure) [2,6,7]. Numerous genetic mutations are necessary for breast cancer development and progression including the acquisition of the capabilities for self-sufficiency in growth signals, insensitivity to anti-growth signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis, known collectively as the "hallmarks of cancer" [8].Numerous molecular targets have been identified as playing a significant role in breast cancer development and progression. Estrogens and the estrogen receptors (ERs) are widely NIH Public Access Author ManuscriptAnticancer Agents Med Chem. Author manuscript; available in PMC 2011 April 12.Published in final edited form as:Anticancer Agents Med Chem. 2008 August ; 8(6): 646-682. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript recognized to play an important role in the development and progression of breast cancer, making estrogens and the ERs widely studied molecular targets [9][10][11][12]. Two of the endogenous estrogens found in humans include estradiol and estrone. In pre-menopausal women, estrogens are produced primarily through conversion of androgens in the ovaries while estrogen production in postmenopausal women occurs in only peripheral tissues [13,14]. Estrogens have various effects throughout the body, including positive effects on the brain, bone, heart, liver, and vagina, with negative effects such as increased risk...

Aromatase and glycosyl transferase inhibiting acridone alkaloids from fruits of Cameroonian Zanthoxylumspecies

“…On the other hand, molecular docking simulation study was performed by AutoDock-Vina software [43]. Aromatase (PDB:3EQM), quinone reductase (PDB: 3G5M) and glycosyltransferase (WAAG) (PDB: 2IW1) target proteins have been used during docking experiments to reveal the binding affinity against anticancer and antibacterial targets, respectively [37,44]. Drug likeness and oral bioavailability of studied compounds were evaluated through Lipinski’s rule of five.…”

Natural Products as Aromatase Inhibitors

“…Isoliquiritigenin (4,2',4'- trihydroxychalcone, 77 ) isolated from licorice ( Glycyrrhiza glabra L.) [141] and tonka bean ( Dipteryx odorata Willd.) [142], was found to be inactive in microsomes [133, 143] but strongly active in SK-BR-3 cells [143]. Isogemichalcone C ( 76 ) was also moderately active in a microsomal assay [135].…”

“…Five of these alkaloids were isolated from Nicotiana tabacum L. [113, 150], with the others from Hydrastis canadensis L. (goldenseal), and Piper L. sp. [143]. None were found to inhibit aromatase.…”

“…coreanus [110] and Urtica dioica L. [155], was tested in microsomes and found to be moderately inhibitory once [110], but otherwise inactive. Another of the triterpenoids tested, aglaiaglabretol B ( 223 ) isolated from Aglaia crassinervia Kurz ex Hiern [159], was moderately active against SK-BR-3 cells [143]. However, aglaiaglabretol B ( 223 ) was also found to be cytotoxic during previous work [159], limiting the potential use of this compound as an aromatase inhibitor.…”

“…(tomatillo, an edible fruit similar to tomato often used in salsa) [162], were found to be inactive against aromatase in microsome testing [143]. …”