scholarly journals Melatonin as an Oncostatic Molecule Based on Its Anti-Aromatase Role in Breast Cancer

2021 ◽  
Vol 22 (1) ◽  
pp. 438
Author(s):  
Yunho Jin ◽  
Yoo Jin Choi ◽  
Kyu Heo ◽  
Seong Joon Park
Keyword(s):  
Breast Cancer ◽  
Developmental Stages ◽  
Therapeutic Option ◽  
Chemotherapeutic Agents ◽  
Common Type ◽  
Aromatase Activity ◽  
Estrogen Synthesis ◽  
Radiation Induced ◽  
Estrogen Biosynthesis

Breast cancer is the most common type of cancer. In the developmental stages of breast cancer, estrogens are strongly involved. As estrogen synthesis is regulated by the enzyme aromatase, targeting the activity of this enzyme represents a therapeutic option. The pineal hormone melatonin may exert a suppressive role on aromatase activity, leading to reduced estrogen biosynthesis. A melatonin-mediated decrease in the expression of aromatase promoters and associated genes would provide suitable evidence of this molecule’s efficacy as an aromatase inhibitor. Furthermore, melatonin intensifies radiation-induced anti-aromatase effects and counteracts the unwanted disadvantages of chemotherapeutic agents. In this manner, this review summarizes the inhibitory role of melatonin in aromatase action, suggesting its role as a possible oncostatic molecule in breast cancer.

scholarly journals Aromatase expression in Xenopus oocytes: a three cell-type model for the ovarian estradiol synthesis

2011 ◽  
Vol 47 (2) ◽  
pp. 241-250 ◽  
Author(s):  
M Gohin ◽  
P Bodinier ◽  
A Fostier ◽  
J Bobe ◽  
F Chesnel
Keyword(s):  
Classical Model ◽  
Biological Significance ◽  
Type Model ◽  
Aromatase Activity ◽  
Steroid Synthesis ◽  
Aromatase Expression ◽  
Androgen Synthesis ◽  
Estrogen Synthesis ◽  
Estradiol Synthesis

In contrast to the classical model describing the synthesis of androgens and estrogens as restricted to somatic cells, a previous study demonstrated that Xenopus laevis oocytes participate in androgen synthesis. The objective of our study was to determine whether Xenopus oocytes are also involved in estrogen synthesis. More precisely, we analyzed aromatase expression by in situ hybridization and RT-QPCR and measured aromatase activity. Aromatase, the enzyme responsible for estrogen synthesis, appears to be expressed and active not only in the follicular cells but also in the vitellogenic oocytes. During late oogenesis, aromatase oocyte expression and activity decreased concomitantly with the trend observed in surrounding follicular layers. In order to investigate the role of estradiol-17β (E2), we studied its effect on oocyte meiotic resumption. It appears that, as in Rana pipiens, E2 inhibited the follicle-enclosed maturation of Xenopus oocytes, likely through inhibition of LH-induced maturation-inducing steroid synthesis. In addition, E2 exerted a slight enhancing action on denuded oocyte maturation whose biological significance remains unclear. Together, our results demonstrate that Xenopus oocyte significantly participates in ovarian E2 synthesis and this may be a common feature of vitellogenic vertebrates.

Role of testosterone synthesized by skin melanocytes in preventing malignant transformation of nevi.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21066-e21066
Author(s):  
Elena Mikhaylovna Frantsiyants ◽  
Valeria Bandovkina ◽  
Yulia A. Pogorelova ◽  
Irina V. Kaplieva ◽  
Natalia D. Cheryarina ◽  
...  
Keyword(s):  
Malignant Transformation ◽  
Cutaneous Melanoma ◽  
Free Testosterone ◽  
Aromatase Activity ◽  
Genotoxic Effects ◽  
Dysplastic Nevi ◽  
Estrogen Synthesis ◽  
Steroid Binding ◽  
Pigmented Nevi

e21066 Background: Melanocytes are involved into the synthesis and metabolism of steroid hormones in the skin. Cutaneous melanoma in 75% of cases occurs in congenital or acquired pigmented nevi. There are no studies comparing local hormonogenesis in nevi and melanomas. The purpose of the study was a comparative analysis of hormone levels in tissues of dysplastic nevi and cutaneous melanoma (pТ1-2N0M0). Methods: Levels of prolactin (PRL), progesterone (P4), total and free testosterone (T and fT), estrone (E1) and estriol (E3) and sex steroid-binding globulin (SSBG) were studied by ELISA in 17 samples of рТ1-2N0M0 melanoma and in 23 samples of dysplastic nevi. Intact tissues (n = 15) obtained from non-cancer patients during surgical treatment was used as the control. Results: Levels of T in nevi, compared to intact tissues, were 1.4 times higher, fT – 8.7 times higher, while SSBG content was 1.9 times lower; E3 was 1.6 times higher, PRL – 1.4 times lower, and levels of E1 in nevi were similar to the values in intact tissues. рТ1-2N0M0 melanomas, compared to intact tissues, demonstrated local androgen imbalance: T levels were decreased by 1.8 times, while fT exceeded the norm by 1.8 times, and SSBG – by 6 times. E1 content increased by 1.6 times, E3 decreased by 2.8 times. The E1/E3 ratio in nevi was reduced by 1.6 times, while in melanoma it was increased by 4.4 times. The T/E1 ratio in nevi was increased by 1.4 times, and in melanoma it was decreased by 2.8 times. Levels of PRL and P4 in melanomas, nevi and in intact tissues did not differ significantly. Conclusions: Melanoma was characterized by hyperestrogenia due to increased levels of E1 and low E3 concentrations which caused malignant transformation of melanocytes. Most likely, in melanoma spent SVT estrone synthesis, as evidenced by increase in the E1 / E3 and decrease T / E1.Apparently, fT in melanoma is used for estrogen synthesis, as indicated by the E1/E3 increase and decrease in the T/E1 ratio. Increased E1 synthesis can contribute to the realization of estrogen genotoxic effects. These mechanisms are absent in tissues of nevi. Hyperandrogenism in nevi probably prevents malignant transformation due to low aromatase activity.

scholarly journals Modulation of in Situ Estrogen Synthesis by Proline-, Glutamic Acid-, and Leucine-Rich Protein-1: Potential Estrogen Receptor Autocrine Signaling Loop in Breast Cancer Cells

2008 ◽  
Vol 22 (3) ◽  
pp. 649-664 ◽  
Author(s):  
Rajib Rajhans ◽  
Hareesh B. Nair ◽  
Sujit S. Nair ◽  
Valerie Cortez ◽  
Kijima Ikuko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Glutamic Acid ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Breast Tumors ◽  
Aromatase Activity ◽  
Aromatase Expression ◽  
Estrogen Synthesis

Abstract In situ estrogen synthesis is implicated in tumor cell proliferation through autocrine or paracrine mechanisms especially in postmenopausal women. Several recent studies demonstrated activity of aromatase, an enzyme that plays a critical role in estrogen synthesis in breast tumors. Proline-, glutamic acid-, and leucine-rich protein-1 (PELP1/MNAR) is an estrogen receptor (ER) coregulator, and its expression is deregulated in breast tumors. In this study, we examined whether PELP1 promotes tumor growth by promoting local estrogen synthesis using breast cancer cells (MCF7) that stably overexpress PELP1. Immunohistochemistry revealed increased aromatase expression in MCF7-PELP1-induced xenograft tumors. Real-time PCR analysis showed enhanced activation of the aromatase promoter in MCF7-PELP1 clones compared with MCF7 cells. Using a tritiated-water release assay, we demonstrated that MCF7-PELP1 clones exhibit increased aromatase activity compared with control MCF-7 cells. PELP1 deregulation uniquely up-regulated aromatase expression via activation of aromatase promoter I.3/II, and growth factor signaling enhanced PELP1 activation of aromatase. PELP1-mediated induction of aromatase requires functional Src and phosphatidylinositol-3-kinase pathways. Mechanistic studies revealed that PELP1 interactions with ER-related receptor-α and proline-rich nuclear receptor coregulatory protein 2 lead to activation of aromatase. Immunohistochemistry analysis of breast tumor array showed increased expression of aromatase in ductal carcinoma in situ and node-positive tumors compared with no or weak expression in normal breast tissue. Fifty-four percent (n = 79) of PELP1-overexpressing tumors also overexpressed aromatase compared with 36% (n = 47) in PELP1 low-expressing tumors. Our results suggest that PELP1 regulation of aromatase represents a novel mechanism for in situ estrogen synthesis leading to tumor proliferation by autocrine loop and open a new avenue for ablating local aromatase activity in breast tumors.

scholarly journals The role of Survivin as a biomarker and potential prognostic factor for breast cancer

2019 ◽  
Vol 65 (6) ◽  
pp. 893-901 ◽  
Author(s):  
Glaucia Luciano da Veiga ◽  
Raissa Daniel Machado da Silva ◽  
Edimar Cristiano Pereira ◽  
Ligia Ajaime Azzalis ◽  
Beatriz da Costa Aguiar Alves ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Chemotherapeutic Agents ◽  
Primary Health ◽  
Common Cancer ◽  
Non Melanoma Skin Cancer ◽  
Potential Prognostic Factor ◽  
Current Scenario ◽  
Melanoma Skin

SUMMARY Breast cancer (BC) is one of the primary health problems worldwide. As the most common cancer in women in the world and in Brasil, behind only non-melanoma skin cancer, this neoplasm corresponds to approximately 28% of new cases per year in the country. BC also affects men, although the incidence corresponds to only 1% of total cases. Currently, most of the chemotherapeutic agents used in BC treatment are extremely toxic and cause long-term side effects. There is also a need to obtain earlier diagnoses, more accurate prognoses and make new therapies available that are more selective and effective in order to improve the current scenario. Therefore, this work sought to evaluate the importance of the biomarker survivin (Sur) in relation to BC, through the detailing of the role of Sur as a biomarker, the correlation between this protein and the prognosis of BC patients, and a summary of therapeutic strategies that target Sur for the development of new anticancer therapies.

Dual Aromatase-Sulphatase Inhibitors (DASIs) for the Treatment of Hormone Dependent Breast Cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Laxmi Banjare ◽  
Akhlesh Kumar Jain ◽  
Suresh Thareja
Keyword(s):  
Breast Cancer ◽  
Dehydroepiandrosterone Sulfate ◽  
Develop Breast Cancer ◽  
Estrone Sulfate ◽  
Cancer Tissues ◽  
Breast Cancer Inhibition ◽  
Estrogen Biosynthesis ◽  
Breast Tissues ◽  
Cancer Inhibition

: Breast cancer is the most frequent diagnosed cancer in women and the second most common form of cancer, causing death after lung cancer, all across the globe at an alarming rate. The level of estrogens, in breast cancer tissues of postmenopausal women is 10-40 folds higher than the non-carcinogenic breast tissues. As a result of this greater level of estrogen, breast tissue becomes more prone to develop breast cancer; mainly estradiol plays a significant role in the initiation and development of hormone dependent breast cancer. Androstenedione, Adrenal dehydroepiandrosterone sulfate and estrone-sulfate also plays an important role of precursor for estrogen biosynthesis. Estrogens deprivation exhibits an attractive phenomena in the advancement of most ideal therapeutics for the treatment of breast cancer. Inhibition of aromatase and sulphatase emerged as attractive therapy for the treatment of hormone dependent breast cancer via deprivation of estrogen by different pathways. The cocktail of aromatase and sulphatase inhibitors known as dual aromatase-sulphatase inhibitors (DASIs) emerged as an attractive approach for the effective estrogen deprivation. The present review article focused on the journey of dual aromatase-sulphatase inhibitors from the beginning to till date (2020). Keeping in view the key observations, this review may be helpful for medicinal chemists to design and develop new and efficient dual aromatase-sulphatase inhibitors for the possible treatment of hormone-related breast cancer.

Treatments for Breast Cancer That Affect Cognitive Function in Postmenopausal Women

2017 ◽  
Vol 4 (2) ◽  
pp. 170-177 ◽  
Author(s):  
Jeffrey D. Blaustein
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Cognitive Function ◽  
Develop Breast Cancer ◽  
Laboratory Animals ◽  
Breast Cancers ◽  
Estrogen Synthesis ◽  
The Brain

About one of every eight women will develop breast cancer during her lifetime. Approximately a quarter of a million new cancer cases are expected in 2017. Of those breast cancers, 60% to 75% will have characteristics suggesting that estrogens are likely to promote growth of those tumors. Consequently, inhibiting estrogen synthesis is one of the main treatments of choice. Therefore, women must understand the potential adverse effects of those treatments on quality of life. This review discusses (a) the role of estrogens locally synthesized in the brain in laboratory animals and women, (b) the effects of estrogens and blockers of estrogen synthesis on cognitive function, and (c) the limitations in experiments on women taking inhibitors. This article aims to provide women and oncologists with information that will encourage them to consider side effects of aromatase inhibitors (AIs) treatment on the brain.

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