The Contribution of Cholesterol and Its Metabolites to the Pathophysiology of Breast Cancer

Baek, Amy E.; Nelson, Erik R.

doi:10.1007/s12672-016-0262-5

Cited by 54 publications

(46 citation statements)

References 125 publications

(143 reference statements)

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“…When the production of CYP27A1 is cut off, it can significantly reduce the distant metastasis of tumor cell-related models [ 121 ]. 27HC can regulate the activity of estrogen receptor alpha (ERα)-positive breast cancer and directly act on immune cells to affect tumor growth and metastasis [ 122 ]. In addition, estrogen produced by adipose tissue also increases the risk of ERα-positive breast cancer.…”

Section: Lipids As Predictors Of Breast Cancer Risk and Prognosismentioning

confidence: 99%

The Function and Mechanism of Lipid Molecules and Their Roles in The Diagnosis and Prognosis of Breast Cancer

et al. 2020

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Lipids are essential components of cell structure and play important roles in signal transduction between cells and body metabolism. With the continuous development and innovation of lipidomics technology, many studies have shown that the relationship between lipids and cancer is steadily increasing, involving cancer occurrence, proliferation, migration, and apoptosis. Breast cancer has seriously affected the safety and quality of life of human beings worldwide and has become a significant public health problem in modern society, with an especially high incidence among women. Therefore, the issue has inspired scientific researchers to study the link between lipids and breast cancer. This article reviews the research progress of lipidomics, the biological characteristics of lipid molecules, and the relationship between some lipids and cancer drug resistance. Furthermore, this work summarizes the lipid molecules related to breast cancer diagnosis and prognosis, and then it clarifies their impact on the occurrence and development of breast cancer The discussion revolves around the current research hotspot long-chain non-coding RNAs (lncRNAs), summarizes and explains their impact on tumor lipid metabolism, and provides more scientific basis for future cancer research studies.

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Section: Lipids As Predictors Of Breast Cancer Risk and Prognosismentioning

confidence: 99%

The Function and Mechanism of Lipid Molecules and Their Roles in The Diagnosis and Prognosis of Breast Cancer

et al. 2020

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“…LXRs are important mediators of cellular cholesterol homeostasis by promoting cholesterol efflux and inhibiting cholesterol synthesis [52]. Several oxysterols and cholesterol metabolites have been identified as LXR agonists.…”

Section: The Importance Of 27hc In Bone Healthmentioning

confidence: 99%

27-Hydroxycholesterol, an endogenous selective estrogen receptor modulator

Nelson

2017

Maturitas

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Estrogen receptors (ERs) mediate the actions of the steroidal estrogens, and are important for the regulation of several physiological and pathophysiological processes, including reproduction, bone physiology, cardiovascular physiology and breast cancer. The unique pharmacology of the ERs allows for certain ligands, such as tamoxifen, to elicit tissue- and context-specific responses, ligands now referred to as selective estrogen receptor modulators (SERMs). Recently, the cholesterol metabolite 27-hydroxychoelsterol (27HC) has been defined as an endogenous SERM, with activities in atherosclerosis, osteoporosis, breast and prostate cancers, and neural degenerative diseases. Since 27HC concentrations closely mirror those of cholesterol, it is possible that 27HC mediates many of the biological effects of cholesterol. This paper provides an overview of ER pharmacology and summarizes the work to date implicating 27HC in various diseases. Wherever possible, we highlight clinical data in support of a role for 27HC in the diseases discussed.

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“…Red clover owers (from which EUG was extracted) were found to inhibit aromatase at low concentrations, while they had estrogenic activity at high concentrations [57]. Moreover, we suggest that the known anti-hyperlipidemic effect of AST [58] may also contribute in its aromatase inhibitory activity [59]. Especially there is a classical correlation between ER-positive breast cancers and adipose tissue expression of aromatase, which is considered a local source of estrogens [60].…”

Section: Discussionmentioning

confidence: 78%

Epigenetic Immunomodulatory Effect of Eugenol and Astaxanthin on Doxorubicin Cytotoxicity in Hormonal Positive Breast Cancer Cells

Fouad

Sayed‐Ahmed

Huwait³

et al. 2020

Preprint

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Background: Hormonal receptor positive (HR+) breast cancer is the most commonly diagnosed molecular subtype of breast cancer; which showed good response to doxorubicin (DOX)-based chemotherapy. Eugenol (EUG) and astaxanthin (AST) are natural compounds with proved epigenetic and immunomodulatory effects in several cancer cell lines. This study has been initiated to improve the cytotoxic activity and reduce resistance of DOX through combination with EUG and AST in MCF7 cells.Methods: Cytotoxic activity of DOX alone and combined with either 1mM EUG or 40µM AST was performed using sulphorhodamine-B assay in MCF7 cells. Global histones acetylation and some immunological markers were investigated using ELISA, western blotting and quantitative RT-PCR techniques. Functional assay of multidrug resistance was performed using rhodamine 123 and Hoechst 3342 dyes. Flow cytometry with annexin V and propidium iodide were used to assess the change in cell cycle and apoptosis along with the expression of some differentiation, apoptosis and autophagy proteins. Results: DOX alone resulted in concentration-dependent cytotoxicity with IC50 of 0.5 μM. Both EUG and AST significantly increased DOX cytotoxicity which is manifested as a significant decrease in DOX IC50 from 0.5 μM to 0.088 μM with EUG and to 0.06 μM with AST. Combinations of DOX with 1mM EUG or 40 µM AST significantly increased the level of histones acetylation and histone acetyl transferase expression, while reduced the expression of aromatase and epidermal growth factor receptor (EGFR) when compared with 0.25 µM DOX alone. Also both combinations showed higher uptake of rhodamine but lower of Hoechst stains, along with increased the percentage of caspase 3, and decreased the expression of CK7 and LC3BI/II ratio. EUG combination induced IFγ but reduced TNFα causing shifting of cells from G2/M to S and G0/ G1 phases. Combination of DOX with EUG induced apoptosis through the higher BAX/ BCl2 ratio, while with AST was through the increase in caspase 8 expressions. Conclusion: EUG and AST potentiated the anticancer activity of DOX through epigenetic histones acetylation along with the immunonomodulation of different apoptotic approaches in MCF7 cells.

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The Contribution of Cholesterol and Its Metabolites to the Pathophysiology of Breast Cancer

Cited by 54 publications

References 125 publications

The Function and Mechanism of Lipid Molecules and Their Roles in The Diagnosis and Prognosis of Breast Cancer

The Function and Mechanism of Lipid Molecules and Their Roles in The Diagnosis and Prognosis of Breast Cancer

27-Hydroxycholesterol, an endogenous selective estrogen receptor modulator

Epigenetic Immunomodulatory Effect of Eugenol and Astaxanthin on Doxorubicin Cytotoxicity in Hormonal Positive Breast Cancer Cells

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