Recent Advancement in Nonsteroidal Aromatase Inhibitors for Treatment of Estrogen-Dependent Breast Cancer

Jiao, Jing; Xiang, Hua; Liao, Qiushi

doi:10.2174/092986710792927877

Cited by 19 publications

(20 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ATG translation initiation site is located on the exon II. There are a number of alternative non-coding first exons (I.1, I.2, I.3, I.4, I.5, I.6, I.7, and PII) which are expressed in tissue-specific manner, lie upstream to the coding region and are spliced to a common acceptor sites in exon 2 [13-15] (Figure 2). The distal promoter I.1 which drives transcription in placenta is located approximately 89 kb upstream of exon II.…”

Section: The Aromatase Gene and Tissue-specific Promoter Expressionmentioning

confidence: 99%

“…Estrogens are suggested to cause breast cancer by stimulating cell growth and proliferation through receptor-mediated processes and via their genotoxic metabolites [29,30]; therefore, inhibition of estrogen production/effect is nowadays a common practice for breast cancer treatment [9]. The general strategies to inhibit estrogen action are to block estrogen receptor (ER) binding to its specific ligand or to disrupt estrogen production by altering the aromatase gene expression or enzyme activities [15]. ER antagonists can block estrogenic actions; however, estrogen production can be inhibited by aromatase inhibitors (AI).…”

Section: Breast Cancer and Aromatasementioning

confidence: 99%

See 1 more Smart Citation

Potential utility of natural products as regulators of breast cancer-associated aromatase promoters

Khan

Zhao

Khan

et al. 2011

Reprod Biol Endocrinol

View full text Add to dashboard Cite

Aromatase, the key enzyme in estrogen biosynthesis, converts androstenedione to estrone and testosterone to estradiol. The enzyme is expressed in various tissues such as ovary, placenta, bone, brain, skin, and adipose tissue. Aromatase enzyme is encoded by a single gene CYP 19A1 and its expression is controlled by tissue-specific promoters. Aromatase mRNA is primarily transcribed from promoter I.4 in normal breast tissue and physiological levels of aromatase are found in breast adipose stromal fibroblasts. Under the conditions of breast cancer, as a result of the activation of a distinct set of aromatase promoters (I.3, II, and I.7) aromatase expression is enhanced leading to local overproduction of estrogen that promotes breast cancer. Aromatase is considered as a potential target for endocrine treatment of breast cancer but due to nonspecific reduction of aromatase activity in other tissues, aromatase inhibitors (AIs) are associated with undesirable side effects such as bone loss, and abnormal lipid metabolism. Inhibition of aromatase expression by inactivating breast tumor-specific aromatase promoters can selectively block estrogen production at the tumor site. Although several synthetic chemical compounds and nuclear receptor ligands are known to inhibit the activity of the tumor-specific aromatase promoters, further development of more specific and efficacious drugs without adverse effects is still warranted. Plants are rich in chemopreventive agents that have a great potential to be used in chemotherapy for hormone dependent breast cancer which could serve as a source for natural AIs. In this brief review, we summarize the studies on phytochemicals such as biochanin A, genistein, quercetin, isoliquiritigenin, resveratrol, and grape seed extracts related to their effect on the activation of breast cancer-associated aromatase promoters and discuss their aromatase inhibitory potential to be used as safer chemotherapeutic agents for specific hormone-dependent breast cancer.

show abstract

Section: The Aromatase Gene and Tissue-specific Promoter Expressionmentioning

confidence: 99%

Section: Breast Cancer and Aromatasementioning

confidence: 99%

Potential utility of natural products as regulators of breast cancer-associated aromatase promoters

Khan

Zhao

Khan

et al. 2011

Reprod Biol Endocrinol

View full text Add to dashboard Cite

show abstract

Section: Recent Advances In the Discovery Of Nonsteroidal Arom Inhmentioning

confidence: 99%

“…118 Vorozole is another older azole compound that causes a reversible inhibition of AROM with IC 50 value of 1.4 nM. 118 The major AROM inhibitory activity of vorozole is attributable to the dextro isomer. Replacement of the 1 H -benzo[ d ][1,2,3]triazole functional group in the vorozole molecule by benzofuran presented a potent racemic triazole derivative with IC 50 value of 10 nM.…”

Section: Recent Advances In the Discovery Of Nonsteroidal Arom Inhmentioning

confidence: 99%

See 1 more Smart Citation

Recent Progress in the Discovery of Next Generation Inhibitors of Aromatase from the Structure–Function Perspective

Ghosh

Egbuta

2016

J. Med. Chem.

View full text Add to dashboard Cite

Human aromatase catalyzes the synthesis of estrogen from androgen with high substrate specificity. For the past 40 years, aromatase has been a target of intense inhibitor discovery research for the prevention and treatment of estrogen-dependent breast cancer. The so-called third generation aromatase inhibitors (AIs) letrozole, anastrozole, and the steroidal exemestane were approved in the U.S. in the late 1990s for estrogen-dependent postmenopausal breast cancer. Efforts to develop better AIs with higher selectivity and lower side effects were handicapped by the lack of an experimental structure of this unique P450. The year 2009 marked the publication of the crystal structure of aromatase purified from human placenta, revealing an androgen-specific active site. The structure has reinvigorated research activities on this fascinating enzyme and served as the catalyst for next generation AI discovery research. Here, we present an account of recent developments in the AI field from the perspective of the enzyme’s structure–function relationships.

show abstract

Nimesulide analogues: From anti-inflammatory to antitumor agents

Catarro

Serrano

Ramos

et al. 2019

Bioorganic Chemistry

View full text Add to dashboard Cite

Recent Advancement in Nonsteroidal Aromatase Inhibitors for Treatment of Estrogen-Dependent Breast Cancer

Cited by 19 publications

References 0 publications

Potential utility of natural products as regulators of breast cancer-associated aromatase promoters

Potential utility of natural products as regulators of breast cancer-associated aromatase promoters

Recent Progress in the Discovery of Next Generation Inhibitors of Aromatase from the Structure–Function Perspective

Nimesulide analogues: From anti-inflammatory to antitumor agents

Contact Info

Product

Resources

About