Interference by Naturally Occurring Fatty Acids in a Noncellular Enzyme-Based Aromatase Bioassay

Balunas, Marcy J.; Su, Bin; Landini, Serena; Brueggemeier, Robert W.; Kinghorn, A. Douglas

doi:10.1021/np050513p

Cited by 26 publications

(32 citation statements)

References 28 publications

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“…Furthermore, unsaturated fatty acids with more than one double bond (e.g., linoleic acid, conjugated linoleic acid, and linolenic acid) are more potent than those with only one double bond (e. g., oleic acid). These results are similar to those reported recently by Balunas et al (49). The article by Balunas et al also indicated that tested unsaturated fatty acids, including linoleic acid, were found to be inactive when tested with in-cell aromatase assay using SK-BR-3 cells.…”

Section: Discussionsupporting

confidence: 91%

Anti-Aromatase Activity of Phytochemicals in White Button Mushrooms (Agaricus bisporus)

et al. 2006

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White button mushrooms (Agaricus bisporous) are a potential breast cancer chemopreventive agent, as they suppress aromatase activity and estrogen biosynthesis. Therefore, we evaluated the activity of mushroom extracts in the estrogen receptor-positive/aromatase-positive MCF-7aro cell line in vitro and in vivo. Mushroom extract decreased testosterone-induced cell proliferation in MCF-7aro cells but had no effect on MCF-10A, a nontumorigenic cell line. Most potent mushroom chemicals are soluble in ethyl acetate. The major active compounds found in the ethyl acetate fraction are unsaturated fatty acids such as linoleic acid, linolenic acid, and conjugated linoleic acid. The interaction of linoleic acid and conjugated linoleic acid with aromatase mutants expressed in Chinese hamster ovary cells showed that these fatty acids inhibit aromatase with similar potency and that mutations at the active site regions affect its interaction with these two fatty acids. Whereas these results suggest that these two compounds bind to the active site of aromatase, the inhibition kinetic analysis indicates that they are noncompetitive inhibitors with respect to androstenedione. Because only conjugated linoleic acid was found to inhibit the testosteronedependent proliferation of MCF-7aro cells, the physiologically relevant aromatase inhibitors in mushrooms are most likely conjugated linoleic acid and its derivatives. The in vivo action of mushroom chemicals was shown using nude mice injected with MCF-7aro cells. The studies showed that mushroom extract decreased both tumor cell proliferation and tumor weight with no effect on rate of apoptosis. Therefore, our studies illustrate the anticancer activity in vitro and in vivo of mushroom extract and its major fatty acid constituents.

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Section: Discussionsupporting

confidence: 91%

Anti-Aromatase Activity of Phytochemicals in White Button Mushrooms (Agaricus bisporus)

et al. 2006

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“…Two other fatty acids, (10E,12Z)-9-hydroxy-10,12-octadecadienoic acid (149) and docosapentaenoic acid (146) [152], showed weak aromatase inhibitory activity in microsomal testing [151]. However, though several unsaturated fatty acids exhibited strong aromatase inhibitiory activity during initial screening they were found to be inactive in cellular aromatase testing [152]. In bioassay-guided studies on natural product extracts for aromatase inhibition activity, fatty acids may be regarded as "interfering" substances, since they are active in noncellular, enzyme-based aromatase assays but do not inhibit aromatase in secondary cellular testing [152].…”

Section: Natural Product Compounds Tested For Aromatase Inhibitionmentioning

confidence: 99%

“…Using the categories delineated above, one of the fatty acids, (10E,12Z)-9-oxo-10,12-octadecadienoic acid (154) isolated from Urtica dioica L. (stinging nettle) showed moderate aromatase inhibitory activity [151]. Two other fatty acids, (10E,12Z)-9-hydroxy-10,12-octadecadienoic acid (149) and docosapentaenoic acid (146) [152], showed weak aromatase inhibitory activity in microsomal testing [151]. However, though several unsaturated fatty acids exhibited strong aromatase inhibitiory activity during initial screening they were found to be inactive in cellular aromatase testing [152].…”

Section: Natural Product Compounds Tested For Aromatase Inhibitionmentioning

confidence: 99%

Natural Products as Aromatase Inhibitors

Balunas¹,

Su²,

Brueggemeier³

et al. 2008

ACAMC

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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...

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“…For instance, plant-derived compounds are widely used as anticancer agents, such as bisin- dole (vinca) alkaloids, camptothecins, epipodophyllotoxins, and taxanes (25). The focus in cancer control has been on the search for safer anticancer agents, with higher patient acceptability.…”

Section: Discussionmentioning

confidence: 99%

CD-200 induces apoptosis and inhibits Bcr-Abl signaling in imatinib-resistant chronic myeloid leukemia with T315I mutation

Fang

Jung

Zhang

et al. 2015

International Journal of Oncology

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Interference by Naturally Occurring Fatty Acids in a Noncellular Enzyme-Based Aromatase Bioassay

Cited by 26 publications

References 28 publications

Anti-Aromatase Activity of Phytochemicals in White Button Mushrooms (Agaricus bisporus)

Anti-Aromatase Activity of Phytochemicals in White Button Mushrooms (Agaricus bisporus)

Natural Products as Aromatase Inhibitors

CD-200 induces apoptosis and inhibits Bcr-Abl signaling in imatinib-resistant chronic myeloid leukemia with T315I mutation

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