Can antioxidant nutraceuticals benefit the menopause?

2002 ◽  
Vol 8 (3) ◽  
pp. 98-101
Author(s):  
Erick Valencia ◽  
Angela Marin ◽  
Gil Hardy
Keyword(s):  
Breast Cancer ◽  
Chronic Diseases ◽  
Prognostic Value ◽  
Literature Search ◽  
Therapeutic Potential ◽  
Nutritional Supplements ◽  
Ageing Population ◽  
Physiological Changes ◽  
Menopausal Women

The antioxidants glutathione, selenium and vitamins C and E meet the criteria for nutraceuticals and their in vivo concentrations can undoubtedly influence and improve many disease processes. In an attempt to quantify and correlate their individual roles as nutritional supplements with their therapeutic potential to improve symptoms and lifestyle during the menopause, we conducted a literature search covering the 15 years up to 2001. Few publications were found dealing specifically with menopausal women. Approximately 90% reported research with vitamins and/or selenium and only one paper investigated a possible correlation between glutathione and breast cancer. This relatively low level of research interest in nutritional or antioxidant aspects of the menopause may just reflect a preoccupation with the more general chronic diseases of an ageing population, without necessarily acknowledging the important physiological changes that occur in women. The little encouraging data in the literature should stimulate more research into the prognostic value, mechanisms and efficacy of nutraceutical supplementation that specifically relate to menopausal women.

scholarly journals Hormone therapy in menopausal women with fibroids: is it safe? (Literature review)

2019 ◽  
Vol 2 (14) ◽  
pp. 38-44
Author(s):  
Ya. Z. Zaydieva
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Hormone Therapy ◽  
Literature Search ◽  
Effective Treatment Option ◽  
Estrogen Receptor Modulators ◽  
Increased Risk ◽  
Menopausal Women ◽  
Receptor Modulators ◽  
Higher Doses

Hormone therapy is an effective treatment option for menopausal women, although prolonged use of hormone therapy is associated with a slightly increased risk of breast cancer, thromboembolism, and stroke. A literature search for studies evaluating the effects of hormone therapy in menopausal women with asymptomatic fibroids demonstrated variable effects of hormone therapy on the volume and size of the fibroids. Some studies have demonstrated an increase in size of pre-existing asymptomatic fibroids and formation of new fibroids with higher doses of progestogen in combination therapy. Selective estrogen receptor modulators having tissue-specific estrogen agonistic and antagonistic actions such as raloxifene have a favorable clinical profile and may be better alternatives in women with asymptomatic fibroids.

scholarly journals Interleukin-19 in Breast Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Ying-Yin Chen ◽  
Chien-Feng Li ◽  
Ching-Hua Yeh ◽  
Ming-Shi Chang ◽  
Chung-Hsi Hsing
Keyword(s):  
Breast Cancer ◽  
Therapeutic Potential ◽  
Endotoxic Shock ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
Duct Carcinoma ◽  
Advanced Tumor ◽  
And Migration

Inflammatory cytokines within the tumor microenvironment are linked to progression in breast cancer. Interleukin- (IL-) 19, part of the IL-10 family, contributes to a range of diseases and disorders, such as asthma, endotoxic shock, uremia, psoriasis, and rheumatoid arthritis. IL-19 is expressed in several types of tumor cells, especially in squamous cell carcinoma of the skin, tongue, esophagus, and lung and invasive duct carcinoma of the breast. In breast cancer, IL-19 expression is correlated with increased mitotic figures, advanced tumor stage, higher metastasis, and poor survival. The mechanisms of IL-19 in breast cancer have recently been explored bothin vitroandin vivo. IL-19 has an autocrine effect in breast cancer cells. It directly promotes proliferation and migration and indirectly provides a microenvironment for tumor progression, which suggests that IL-19 is a prognostic marker in breast cancer and that antagonizing IL-19 may have therapeutic potential.

In-silico Design, ADMET Screening, MM-GBSA Binding Free Energy of Some Novel Isoxazole Substituted 9-Anilinoacridines as HER2 Inhibitors Targeting Breast Cancer

2019 ◽  
Vol 11 (2) ◽  
pp. 118-128 ◽  
Author(s):  
Rajagopal Kalirajan ◽  
Arumugasamy Pandiselvi ◽  
Byran Gowramma ◽  
Pandiyan Balachandran
Keyword(s):  
Breast Cancer ◽  
Free Energy ◽  
In Silico ◽  
Therapeutic Potential ◽  
Binding Free Energy ◽  
Breast Cancers ◽  
Molecular Docking Study ◽  
In Silico Admet

Background: Human Epidermal development factor Receptor-2 (HER2) is a membrane tyrosine kinase which is overexpressed and gene amplified in human breast cancers. HER2 amplification and overexpression have been linked to important tumor cell proliferation and survival pathways for 20% of instances of breast cancer. 9-aminoacridines are significant DNA-intercalating agents because of their antiproliferative properties. Objective: Some novel isoxazole substituted 9-anilinoacridines(1a-z) were designed by in-silico technique for their HER2 inhibitory activity. Docking investigations of compounds 1a-z are performed against HER2 (PDB id-3PP0) by using Schrodinger suit 2016-2. Methods: Molecular docking study for the designed molecules 1a-z are performed by Glide module, in-silico ADMET screening by QikProp module and binding free energy by Prime-MMGBSA module of Schrodinger suit. The binding affinity of designed molecules 1a-z towards HER2 was chosen based on GLIDE score. Results: Many compounds showed good hydrophobic communications and hydrogen bonding associations to hinder HER2. The compounds 1a-z, aside from 1z have significant Glide scores in the scope of - 4.91 to - 10.59 when compared with the standard Ethacridine (- 4.23) and Tamoxifen (- 3.78). The in-silico ADMET properties are inside the suggested about drug likeness. MM-GBSA binding of the most intense inhibitor is positive. Conclusion: The outcomes reveal that this study provides evidence for the consideration of isoxazole substituted 9-aminoacridine derivatives as potential HER2 inhibitors. The compounds, 1s,x,v,a,j,r with significant Glide scores may produce significant anti breast cancer activity and further in vitro and in vivo investigations may prove their therapeutic potential.

scholarly journals SHP2 is a multifunctional therapeutic target in drug resistant metastatic breast cancer

Oncogene ◽  
2020 ◽  
Vol 39 (49) ◽  
pp. 7166-7180
Author(s):  
Hao Chen ◽  
Sarah Libring ◽  
Kasi Viswanatharaju Ruddraraju ◽  
Jinmin Miao ◽  
Luis Solorio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Kinase Inhibitor ◽  
Therapeutic Potential ◽  
Tyrosine Phosphatase ◽  
3D Culture ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Growth And Survival

AbstractMetastatic breast cancer (MBC) is an extremely recalcitrant disease capable of bypassing current targeted therapies via engagement of several growth promoting pathways. SH2 containing protein tyrosine phosphatase-2 (SHP2) is an oncogenic phosphatase known to facilitate growth and survival signaling downstream of numerous receptor inputs. Herein, we used inducible genetic depletion and two distinct pharmacological inhibitors to investigate the therapeutic potential of targeting SHP2 in MBC. Cells that acquired resistance to the ErbB kinase inhibitor, neratinib, displayed increased phosphorylation of SHP2 at the Y542 activation site. In addition, higher levels of SHP2 phosphorylation, but not expression, were associated with decreased survival of breast cancer patients. Pharmacological inhibition of SHP2 activity blocked ERK1/2 and AKT signaling generated from exogenous stimulation with FGF2, PDGF, and hGF and readily prevented MBC cell growth induced by these factors. SHP2 was also phosphorylated upon engagement of the extracellular matrix (ECM) via focal adhesion kinase. Consistent with the potential of SHP2-targeted compounds as therapeutic agents, the growth inhibitory property of SHP2 blockade was enhanced in ECM-rich 3D culture environments. In vivo blockade of SHP2 in the adjuvant setting decreased pulmonary metastasis and extended the survival of systemic tumor-bearing mice. Finally, inhibition of SHP2 in combination with FGFR-targeted kinase inhibitors synergistically blocked the growth of MBC cells. Overall, our findings support the conclusion that SHP2 constitutes a shared signaling node allowing MBC cells to simultaneously engage a diversity of growth and survival pathways, including those derived from the ECM.

scholarly journals Loss of Proprotein Convertase Furin in Mammary Gland Impairs proIGF1R and proIR Processing and Suppresses Tumorigenesis in Triple Negative Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2686
Author(s):  
Zongsheng He ◽  
Abdel-Majid Khatib ◽  
John W. M. Creemers
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Mouse Model ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Therapeutic Potential ◽  
Mammary Development ◽  
Proprotein Convertase

In triple negative breast cancer (TNBC) cell lines, the proprotein convertase Furin cleaves and then activates several protein precursors involved in oncogenesis. However, the in vivo role of Furin in the mammary gland and how mammary gland-specific Furin knockout specifically influences tumor initiation and progression of TNBC is unknown. Here, we report that Furin is frequently overexpressed in TNBC tumors and this correlates with poor prognosis in patients with TNBC tumors. In a whey acidic protein (WAP)-induced mammary epithelial cell-specific Furin knockout mouse model, mice show normal mammary development. However, loss of Furin in mammary glands inhibits primary tumor growth and lung metastasis in an oncogene-induced TNBC mouse model. Further analysis of TNBC mice lacking Furin revealed repressed maturation of the Furin substrates proIGF1R and proIR that are associated with reduced expression and activation of their downstream effectors PI3K/AKT and MAPK/ERK1/2. In addition, these tissues showed enhanced apoptotic signaling. In conclusion, our findings reveal that upregulated Furin expression reflects the poor prognosis of TNBC patients and highlights the therapeutic potential of inhibiting Furin in TNBC tumors.

scholarly journals BIOLOGICAL POTENTIAL OF BENZOXAZOLE DERIVATIVES: AN UPDATED REVIEW

2020 ◽  
pp. 28-41
Author(s):  
UDDIN KAMAL ◽  
NAIM MOHD JAVED ◽  
KUMAR ARUN
Keyword(s):  
Antimicrobial Activity ◽  
Literature Search ◽  
Therapeutic Potential ◽  
Anthelmintic Activity ◽  
Pharmacological Activities ◽  
Drug Molecules ◽  
Biological Potential ◽  
Derivatives Of ◽  
Heterocyclic Moiety

Objective: Heterocycles exhibited an extensive role in the medicinal chemistry for the development of pharmaceutically active molecules. A heterocyclic scaffold is responsible for the therapeutic potential of majority of synthesized drug molecules. Therapeutic changes in the drug molecules related to the slight changes in the heterocyclic moiety. Benzoxazole and its derivatives showed potent and significant pharmacological activities. The main objective of our study is to impart updated information about synthesized benzoxazole derivatives and their biological potential against numerous diseases. Methods: A literature search was directed on the databases, namely, in MDPI, Science direct, PubMed, Springer, Taylor, and Francis by searching different keywords “Benzoxazole,” antimicrobial activity, anticancer activity, antitubercular, anti-inflammatory, analgesic, and anthelmintic activity. Conclusion: This review may radiate the path of researchers that are working to synthesized novel benzoxazole derivatives in the prospects of effectiveness and safety. Nonetheless, further in vivo and clinical studies are warranted on the potential derivatives of benzoxazole.

scholarly journals A Targeted-Covalent Inhibitor of 17β-HSD1 Blocks Two Estrogen-Biosynthesis Pathways: In Vitro (Metabolism) and In Vivo (Xenograft) Studies in T-47D Breast Cancer Models

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1841
Author(s):  
Donald Poirier ◽  
Jenny Roy ◽  
René Maltais
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Therapeutic Potential ◽  
Tumor Model ◽  
Growth Effect ◽  
Mouse Tumor ◽  
Cancer Models ◽  
Model Cell

17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) plays an important role in estrogen-dependent breast tumor growth. In addition to being involved in the production of estradiol (E2), the most potent estrogen in women, 17β-HSD1 is also responsible for the production of 5-androsten-3β,17β-diol (5-diol), a weaker estrogen than E2, but whose importance increases after menopause. 17β-HSD1 is therefore a target of choice for the treatment of estrogen-dependent diseases such as breast cancer and endometriosis. After we developed the first targeted-covalent (irreversible) and non-estrogenic inhibitor of 17β-HSD1, a molecule named PBRM, our goal was to demonstrate its therapeutic potential. Enzymatic assays demonstrated that estrone (E1) and dehydroepiandrosterone (DHEA) were transformed into E2 and 5-diol in T-47D human breast cancer cells, and that PBRM was able to block these transformations. Thereafter, we tested PBRM in a mouse tumor model (cell-derived T-47D xenografts). After treatment of ovariectomized (OVX) mice receiving E1 or DHEA, PBRM given orally was able to reduce the tumor growth at the control (OVX) level without any observed toxic effects. Thanks to its irreversible type of inhibition, PBRM retained its anti-tumor growth effect, even after reducing its frequency of administration to only once a week, a clear advantage over reversible inhibitors.

scholarly journals Targeted Transdermal Delivery of Curcumin for Breast Cancer Prevention

2019 ◽  
Vol 16 (24) ◽  
pp. 4949 ◽  
Author(s):  
Michele Atlan ◽  
Josh Neman
Keyword(s):  
Breast Cancer ◽  
Cancer Prevention ◽  
Transdermal Delivery ◽  
Therapeutic Potential ◽  
Preventive Measure ◽  
Breast Cancer Prevention ◽  
Herbal Supplement ◽  
Global Challenge ◽  
Research Concept

N.B. This manuscript is based on the research concept submitted to the “Global Challenge to Prevent Breast Cancer” idea showcase and competition, launched in 2018 by the California Breast Cancer Research Program (CBCRP), which was subsequently selected for publication. The hypothesis, methods, and discussion put forth here are thus proposed concept studies, which could eventually be elucidated in the future. Curcumin is an herbal supplement, shown in preclinical studies to have antioxidant, anti-inflammatory, and antitumoral properties that we believe can be harnessed for breast cancer prevention. However, due to its poor absorption when consumed orally, curcumin’s anticancer effects have not yet been exploited to their full therapeutic potential. Incorporating existing research that focuses on the optimization of curcumin’s bioavailability and the latest transdermal delivery technology, we propose, below, a hypothetical in vivo study to test whether a targeted daily dose of bioavailable curcumin has a cytotoxic effect on cancer cells, potentially reducing the incidence of breast cancer over time. Our ultimate objective is to adopt innovative methods to create curcumin-infused bio-textiles offering transdermal, targeted drug delivery, simply through contact with the skin. We would use this fabric to create disposable bra inserts for an effortless, daily breast cancer prevention regimen for healthy women. It would be essential that the cost of these inserts remain reasonable, but if successful, curcumin is readily available, affordable and non-toxic, and could thus be a preventive measure that would be beneficial for women from all socio-economic backgrounds.

scholarly journals BRD4 modulates vulnerability of triple-negative breast cancer to targeting of integrin-dependent signaling pathways

2020 ◽  
Vol 43 (6) ◽  
pp. 1049-1066
Author(s):  
Yang Zhang ◽  
Bingwei Xu ◽  
Junfeng Shi ◽  
Jieming Li ◽  
Xinlan Lu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcomes ◽  
Cell Lines ◽  
Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Therapeutic Potential ◽  
Apoptotic Cell ◽  
Xenograft Model

Abstract Purpose Stemming from a myriad of genetic and epigenetic alterations, triple-negative breast cancer (TNBC) is tied to poor clinical outcomes and aspires for individualized therapies. Here we investigated the therapeutic potential of co-inhibiting integrin-dependent signaling pathway and BRD4, a transcriptional and epigenetic mediator, for TNBC. Methods Two independent patient cohorts were subjected to bioinformatic and IHC examination for clinical association of candidate cancer drivers. The efficacy and biological bases for co-targeting these drivers were interrogated using cancer cell lines, a protein kinase array, chemical inhibitors, RNAi/CRISPR/Cas9 approaches, and a 4 T1-Balb/c xenograft model. Results We found that amplification of the chromosome 8q24 region occurred in nearly 20% of TNBC tumors, and that it coincided with co-upregulation or amplification of c-Myc and FAK, a key effector of integrin-dependent signaling. This co-upregulation at the mRNA or protein level correlated with a poor patient survival (p < 0.0109 or p < 0.0402, respectively). Furthermore, we found that 14 TNBC cell lines exhibited high vulnerabilities to the combination of JQ1 and VS-6063, potent pharmacological antagonists of the BRD4/c-Myc and integrin/FAK-dependent pathways, respectively. We also observed a cooperative inhibitory effect of JQ1 and VS-6063 on tumor growth and infiltration of Ly6G+ myeloid-derived suppressor cells in vivo. Finally, we found that JQ1 and VS-6063 cooperatively induced apoptotic cell death by altering XIAP, Bcl2/Bcl-xl and Bim levels, impairing c-Src/p130Cas-, PI3K/Akt- and RelA-associated signaling, and were linked to EMT-inducing transcription factor Snail- and Slug-dependent regulation. Conclusion Based on our results, we conclude that the BRD4/c-Myc- and integrin/FAK-dependent pathways act in concert to promote breast cancer cell survival and poor clinical outcomes. As such, they represent promising targets for a synthetic lethal-type of therapy against TNBC.

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