Phytochemicals for breast cancer prevention by targeting aromatase

Adams, Lowell; Chen, Shiuan

doi:10.2741/3493

Cited by 32 publications

(28 citation statements)

References 82 publications

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“…Exemestane is highly effective in inhibiting estrogen biosynthesis, as is well illustrated in peripheral fat, which is the principal site of estrogen biosynthesis in postmenopausal women (34). We have shown in this paper that, unexpectedly, exemestane exerts a wide range of other biological effects, seemingly mechanistically unrelated to aromatase inhibition, among which the up-regulation of the Keap1-Nrf2-ARE cytoprotective signaling system is probably the most prominent.…”

Section: Discussionmentioning

confidence: 66%

Relevance of anti-inflammatory and antioxidant activities of exemestane and synergism with sulforaphane for disease prevention

Liu

Talalay

2013

Proc. Natl. Acad. Sci. U.S.A.

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Exemestane (6-methyleneandrosta-1,4-diene-3,17-dione) is a synthetic steroidal inhibitor of the aromatase reaction that catalyzes the terminal and rate-limiting step of the biosynthesis of estrogens. It is active clinically in preventing, delaying progression of, and treating mammary cancers, many of which are estrogen receptor-positive. A striking feature of the structure of exemestane is an extended system of conjugated Michael reaction functions, which is also characteristic of inducers of a broad network of chemoprotective genes regulated by the Keap1 (Kelch-like ECAassociated protein)/Nrf2 (nuclear factor E2-related factor 2)/ARE (antioxidant response element) signaling system. These genes are largely involved in xenobiotic metabolism and antioxidative and anti-inflammatory protection, as well as the synthesis and reduction of glutathione. We show here that exemestane transcriptionally activates NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1), typical chemoprotective gene products, in a wide variety of mouse, rat, and human cells. It protects several cell lines against oxidative toxicity of tert-butyl hydroperoxide and 4-hydroxynonenal, against free radical damage arising from hypoxia-reoxygenation, and against UVA radiation damage. Exemestane also inhibits the inflammatory increases in inducible nitric oxide synthase (iNOS) in mouse macrophages exposed to LPS (lipopolysaccharide), thereby resembling the isothiocyanate sulforaphane derived from broccoli. Remarkably, combinations of exemestane and sulforaphane act highly synergistically, and this property is also displayed by several other phytochemicals. Thus, exemestane has a wide range of previously unrecognized protective activities, probably unrelated to aromatase inhibition. Its potential for reducing the risk, not only of breast cancer, but also of other chronic diseases that arise from inflammation, oxidative stress, and DNA-damaging electrophiles, requires exploration, particularly in view of the synergism with other phytochemicals.

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Section: Discussionmentioning

confidence: 66%

Relevance of anti-inflammatory and antioxidant activities of exemestane and synergism with sulforaphane for disease prevention

Liu

Talalay

2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Polyphenols are bioactive compounds and have been reported to potentially exert anticancer effects via a variety of mechanisms, including the removal of carcinogenic agents2829, modulation of cancer cell signaling3334 and cell cycle progression3536, promotion of apoptosis373839 and modulation of enzymatic activities40.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant and Antitumor Activity of a Bioactive Polyphenolic Fraction Isolated from the Brewing Process

Tatullo

Simone

Tarullo

et al. 2016

Sci Rep

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There is increasing interest in identifying natural bioactive compounds that can improve mitochondrial functionality and regulate apoptosis. The brewery industry generates wastewater that could yield a natural extract containing bioactive phenolic compounds. Polyphenols act as antioxidants and have been documented to protect the human body from degenerative diseases such as cardiovascular diseases or cancer. The main aims of our research were to determine the phenolic profile of a crude extract obtained (at pilot scale) from a brewery waste stream and to evaluate the biochemical activity of this extract on the mitochondrial function of a cancer cell line (SH-SY5Y). This work is a basic translational pilot study. The total phenolic content was determined by the Folin–Ciocalteu assay, which revealed that 2.30% of the extract consisted of phenolic compounds. The polyphenols, identified and quantified by reverse-phase-high-performance liquid chromatography and mass spectrometry (RP-HPLC/MS), were mainly flavonoids. After cell culture, the tumoral cells treated with the polyphenolic extract showed enhanced mitochondrial oxidative function, which is likely related to a decrease in oxidative stress and an increase in mitochondrial biogenesis. This type of brewery waste stream, properly treated, may be a promising source of natural antioxidants to replace the synthetic antioxidants currently used in the food industry.

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“…These include removal of carcinogenic agents [79], modulation of cancer cell signaling [80] cell cycle progression [81], promotion of apoptosis [82] and modulation of enzymatic activities [83]. For example, polyphenols influence the metabolism of pro-carcinogens by modulating the expression of cytochrome P450 enzymes involved in their activation to carcinogens.…”

Section: Polyphenols and Cancermentioning

confidence: 99%

Natural plant polyphenols for alleviating oxidative damage in man: Current status and future perspectives

Li¹,

Liu²,

Шен³

et al. 2016

Trop. J. Pharm Res

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Phytochemicals for breast cancer prevention by targeting aromatase

Cited by 32 publications

References 82 publications

Relevance of anti-inflammatory and antioxidant activities of exemestane and synergism with sulforaphane for disease prevention

Relevance of anti-inflammatory and antioxidant activities of exemestane and synergism with sulforaphane for disease prevention

Antioxidant and Antitumor Activity of a Bioactive Polyphenolic Fraction Isolated from the Brewing Process

Natural plant polyphenols for alleviating oxidative damage in man: Current status and future perspectives

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