Comparative Analysis of Biological Effects of Selective Activator of the Glucocorticoid Receptor Cpda on Different Subtypes of Breast Cancer Cell Lines

Zhidkova, Ekaterina M.; Кузин, К. А.; Тилова, Л Р; Savinkova, Alena V.; Борисова, О Ю; Лаврова, М. Д.; Maksimova, Varvara; Кирсанов, Кирилл И.; Якубовская, М. Г.; Лесовая, Е. А.

doi:10.21294/1814-4861-2017-16-6-41-46

Cited by 6 publications

(3 citation statements)

References 3 publications

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“…It has been shown that a SEGRA of natural origin, CpdA, effectively inhibited the growth and proliferation of MDA-MB-231 and MCF7 cells, did not promote drug resistance and did not attenuate the cytotoxicity of the main therapeutics. 68,69 Similar observations were described for another SEGRA, rigid steroid 21-hydroxy-6,19-epoxyprogesterone. 70 However, no data are yet available on the specific SEGRA effects on key components of cell motility, migration, EMT, and metastatic potential.…”

Section: Selective Activation Of Gr In Bc Metastasissupporting

confidence: 70%

“… 44 , 47 The therapeutic anti-inflammatory and anticancer efficacy of different SEGRAs has been confirmed in multiple studies. 44 , 47 , 68 , 69 However, data on the possible implications of SEGRAs in the treatment of metastatic BC are insufficient. It has been shown that a SEGRA of natural origin, CpdA, effectively inhibited the growth and proliferation of MDA-MB-231 and MCF7 cells, did not promote drug resistance and did not attenuate the cytotoxicity of the main therapeutics.…”

Section: Selective Activation Of Gr In Bc Metastasismentioning

confidence: 99%

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A Brief Overview of the Paradoxical Role of Glucocorticoids in Breast Cancer

Zhidkova¹,

Lylova²,

Savinkova³

et al. 2020

Breast Cancer�(Auckl)

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Glucocorticoids (GCs) are stress hormones that play multiple roles in the regulation of cancer cell differentiation, apoptosis, and proliferation. Some types of cancers, such as hematological malignancies, can be effectively treated by GCs, whereas the responses of epithelial cancers to GC treatment vary, even within cancer subtypes. In particular, GCs are frequently used as supporting treatment of breast cancer (BC) to protect against chemotherapy side effects. In the therapy of nonaggressive luminal subtypes of BC, GCs can have auxiliary antitumor effects due to their cytotoxic actions on cancer cells. However, GCs can promote BC progression, colonization of distant metastatic sites, and metastasis. The effects of GCs on cell proliferation vary with BC subtype and its molecular profile and are realized via the activation of glucocorticoid receptor (GR), a well-known transcriptional factor involved in the regulation of the expression of multiple genes, cell-cell adhesion, and cell migration and polarity. This review focuses on the roles of GC signaling in the adhesion, migration, and metastasis of BC cells. We discuss the molecular mechanisms of GC actions that lead to BC metastasis and propose alternative pharmacological uses of GCs for BC treatment.

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Section: Selective Activation Of Gr In Bc Metastasissupporting

confidence: 70%

Section: Selective Activation Of Gr In Bc Metastasismentioning

confidence: 99%

A Brief Overview of the Paradoxical Role of Glucocorticoids in Breast Cancer

Zhidkova¹,

Lylova²,

Savinkova³

et al. 2020

Breast Cancer�(Auckl)

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show abstract

“…CpdA, a well-characterized SEGRA, is a synthetic analog of a natural compound found in Salsola tuberculatiformis Botschantzev and exerts GR-dependent anti-inflammatory and anti-cancer effects [16,41,62,63]. CpdA appears to be a promising alternative to GCs with fewer side effects [18,41,51,62,[64][65][66].…”

Section: Chemical and Pharmacological Features Of Cpda And Its Target...mentioning

confidence: 99%

Synephrine and Its Derivative Compound A: Common and Specific Biological Effects

Dodonova,

Zhidkova,

Kryukov

et al. 2023

IJMS

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This review is focused on synephrine, the principal phytochemical found in bitter orange and other medicinal plants and widely used as a dietary supplement for weight loss/body fat reduction. We examine different aspects of synephrine biology, delving into its established and potential molecular targets, as well as its mechanisms of action. We present an overview of the origin, chemical composition, receptors, and pharmacological properties of synephrine, including its anti-inflammatory and anti-cancer activity in various in vitro and animal models. Additionally, we conduct a comparative analysis of the molecular targets and effects of synephrine with those of its metabolite, selective glucocorticoid receptor agonist (SEGRA) Compound A (CpdA), which shares a similar chemical structure with synephrine. SEGRAs, including CpdA, have been extensively studied as glucocorticoid receptor activators that have a better benefit/risk profile than glucocorticoids due to their reduced adverse effects. We discuss the potential of synephrine usage as a template for the synthesis of new generation of non-steroidal SEGRAs. The review also provides insights into the safe pharmacological profile of synephrine.

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Inhibition of glucocorticoid-induced REDD1 expression by rapamycin in breast cancer cells

et al. 2022

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Introduction. Glucocorticoids are often used in combination therapy for breast cancer as an adjuvant to increase therapeutic effects of the main cytotoxic drug and to reduce side effects of chemotherapy. However, glucocorticoids can cause serious complications and trigger tumor progression. In the last decade, it was found that side effects from glucocorticoids are mediated by an increase in REDD1 gene expression. Using this knowledge, we have developed a new chemotherapeutic strategy for blood cancers aimed at reducing adverse events from glucocorticoids. Successful experiments with a combination of glucocorticoids and REDD1 expression inhibitors on the models of blood tumors allowed us to use this regimen for the treatment of certain subtypes of breast cancer.Objective: to optimize the algorithm of breast cancer cell treatment with a combination of glucocorticoids and REDD1 expression inhibitors on the example of rapamycin.Materials and methods. We used the MCF-7 and MDA-MB-231 breast cancer cell lines. The antiproliferative activity was estimated by direct cell count; REDD1 expression was measured using western blotting and quantitative polymerase chain reaction.Results. We found that rapamycin can inhibit both baseline and glucocorticoids induced REDD1 expression in the cells of luminal and triple negative breast cancer. The drug demonstrated lower ability to inhibit the viability of breast cancer cells than that of leukemia and lymphoma cells.Conclusion. Inhibited proliferation of breast cancer cells after their incubation with rapamycin and dexamethasone, as well as the ability of rapamycin to reduce basal and glucocorticoid-induced REDD1 expression in breast cancer cells suggest the importance of studies analyzing the impact of combinations that include glucocorticoids and REDD1 expression inhibitors from the class of PI3K/Akt/mTOR signaling pathway modulators (phosphoinositide-3-kinase/α-serine-threonine kinase/mammalian rapamycin target) on breast cancer cells.

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Comparative Analysis of Biological Effects of Selective Activator of the Glucocorticoid Receptor Cpda on Different Subtypes of Breast Cancer Cell Lines

Cited by 6 publications

References 3 publications

A Brief Overview of the Paradoxical Role of Glucocorticoids in Breast Cancer

A Brief Overview of the Paradoxical Role of Glucocorticoids in Breast Cancer

Synephrine and Its Derivative Compound A: Common and Specific Biological Effects

Inhibition of glucocorticoid-induced REDD1 expression by rapamycin in breast cancer cells

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