scholarly journals Combined Effects of Eicosapentaenoic Acid and Adipocyte Renin–Angiotensin System Inhibition on Breast Cancer Cell Inflammation and Migration

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 220 ◽  
Author(s):  
Fahmida Rasha ◽  
Chanaka Kahathuduwa ◽  
Latha Ramalingam ◽  
Arelys Hernandez ◽  
Hanna Moussa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Eicosapentaenoic Acid ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Anti Inflammatory ◽  
And Migration

Obesity is a major risk factor for breast cancer (BC). Obesity-related metabolic alterations such as inflammation and overactivation of the adipose renin–angiotensin system (RAS) may contribute to the progression of BC. Clinically used antihypertensive drugs such as angiotensin-converting enzyme inhibitors (ACE-I) and dietary bioactive components such as eicosapentaenoic acid (EPA) are known for their anti-inflammatory and adipose RAS blocking properties. However, whether EPA enhances the protective effects of ACE-I in lessening adipocyte inflammation on BC cells has not been studied. We hypothesized that combined EPA and ACE-I would attenuate BC cell inflammation and migration possibly via adipose RAS inhibition. To test our hypothesis, we examined the (i) direct effects of an ACE-I (captopril (CAP)) or EPA, individually and combined, on MCF-7 and MDA-MB-231 human BC cells, and the (ii) effects of conditioned medium (CM) from human adipocytes pretreated with the abovementioned agents on BC cells. We demonstrated that CM from adipocytes pretreated with EPA with or without captopril (but not direct treatments of BC cells) significantly reduced proinflammatory cytokines expression in both BC cell lines. Additionally, cell migration was reduced in MDA-MB-231 cells in response to both direct and CM-mediated CAP and/or EPA treatments. In summary, our study provides a significant insight into added benefits of combining anti-inflammatory EPA and antihypertensive ACE-I to attenuate the effects of adipocytes on breast cancer cell migration and inflammation.

Renin angiotensin system inhibition attenuates adipocyte-breast cancer cell interactions

2020 ◽  
Vol 394 (1) ◽  
pp. 112114 ◽  
Author(s):  
Fahmida Rasha ◽  
Latha Ramalingam ◽  
Kalhara Menikdiwela ◽  
Arelys Hernandez ◽  
Hanna Moussa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Renin Angiotensin System ◽  
Cell Interactions ◽  
Angiotensin System ◽  
Renin Angiotensin

Characterization of YY1 OPB Peptide for its Anticancer Activity

2019 ◽  
Vol 19 (6) ◽  
pp. 504-511 ◽  
Author(s):  
Yige Qi ◽  
Ting Yan ◽  
Lu Chen ◽  
Qiang Zhang ◽  
Weishu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Amino Acids ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Expression Vectors ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Oncogene Products ◽  
And Migration

Background:The oncoprotein binding (OPB) domain of Yin Yang 1 (YY1) consists of 26 amino acids between G201 and S226, and is involved in YY1 interaction with multiple oncogene products, including MDM2, AKT, EZH2 and E1A. Through the OPB domain, YY1 promotes the oncogenic or proliferative regulation of these oncoproteins in cancer cells. We previously demonstrated that a peptide with the OPB sequence blocked YY1-AKT interaction and inhibited breast cancer cell proliferation.Objective:In the current study, we characterized the OPB domain and determined a minimal region for peptide design to suppress cancer cellMethods:Using alanine-scan method, we identified that the amino acids at OPB C-terminal are essential to YY1 binding to AKT. Further studies suggested that serine and threonine residues, but not lysines, in OPB play a key role in YY1-AKT interaction. We generated GFP fusion expression vectors to express OPB peptides with serially deleted N-terminal and found that OPB1 (i.e. G201-S226) is cytoplasmic, but OPB2 (i.e. E206-S226), OPB3 (i.e. E206-S226) and control peptide were both nuclear and cytoplasmic.Results:Both OPB1 and 2 inhibited breast cancer cell proliferation and migration, but OPB3 exhibited similar effects to control. OPB1 and 2 caused cell cycle arrest at G1 phase, increased p53 and p21 expression, and reduced AKT(S473) phosphorylation in MCF-7 cells, but not in MDA-MB-231 cells.Conclusion:: Overall, the serines and threonines of OPB are essential to YY1 binding to oncoproteins, and OPB peptide can be minimized to E206-S226 that maintain inhibitory activity to YY1- promoted cell proliferation.

A Review on Phytopharmaceutical shaving Concomitant Experimental Anti-Diabetic and Anti-Cancer Effects as Potential Sources for Targeted Therapies Against Insulin Mediated Breast Cancer Cell Invasion and Migration

2020 ◽  
Vol 16 ◽  
Author(s):  
Vibhavana Singh ◽  
Rakesh Reddy ◽  
Antarip Sinha ◽  
Venkatesh Marturi ◽  
Shravani Sripathi Panditharadyula ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Medicinal Plants ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Invasion ◽  
Breast Tumor ◽  
Cancer Cell Invasion ◽  
Invasion And Migration ◽  
Anti Cancer ◽  
And Migration

: Diabetes and breast cancer are pathophysiologically similar and clinically established diseases that co-exist with a wider complex similar molecular signalling and having similar set of risk factors. Insulin plays a pivotal role for invasion and migration of breast cancer cells. Several ethnopharmacological evidences light the concomitant anti-diabetic and anti-cancer activity of medicinal plant and phytochemicals against breast tumor of patients with diabetes. This present article reviewed the findings on medicinal plants and phytochemicals with concomitant anti-diabetic and anti-cancer effects reported in scientific literature to facilitate the development of dual-acting therapies against diabetes and breast cancer. The schematic tabular form of published literatures on medicinal plants (63 plants belongs to 45 families) concluded the dynamics of phytochemicals against diabetes and breast tumor that could be explored further for the discovery of therapies for controlling of breast cancer cell invasion and migration in patient with diabetes.

scholarly journals Long non-coding RNA ARHGAP5-AS1 inhibits migration of breast cancer cell via stabilizing SMAD7 protein

2021 ◽  
Author(s):  
Chen-Long Wang ◽  
Jing-Chi Li ◽  
Ci-Xiang Zhou ◽  
Cheng-Ning Ma ◽  
Di-Fei Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Rho Gtpase ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Breast Cancer Cell Lines ◽  
Smad7 Protein

Abstract Purpose Tumor metastasis is the main cause of death from breast cancer patients and cell migration plays a critical role in cancer metastasis. Recent studies have shown long non-coding RNAs (lncRNAs) play an essential role in the initiation and progression of cancer. In the present study, the role of an LncRNA, Rho GTPase Activating Protein 5- Antisense 1 (ARHGAP5-AS1) in breast cancer was investigated. Methods RNA sequencing was performed to find out dysregulated LncRNAs in MDA-MB-231-LM2 cells. Transwell migration assays and F-actin staining were utilized to estimate cell migration ability. RNA pulldown assays and RNA immunoprecipitation were used to prove the interaction between ARHGAP5-AS1 and SMAD7. Western blot and immunofluorescence imaging were used to examine the protein levels. Dual luciferase reporter assays were performed to evaluate the activation of TGF-β signaling. Results We analyzed the RNA-seq data of MDA-MB-231 and its highly metastatic derivative MDA-MB-231-LM2 cell lines (referred to as LM2) and identified a novel lncRNA (NR_027263) named as ARHGAP5-AS1, which expression was significantly downregulated in LM2 cells. Further functional investigation showed ARHGAP5-AS1 could inhibit cell migration via suppression of stress fibers in breast cancer cell lines. Afterwards, SMAD7 was further identified to interact with ARHGAP5-AS1 by its PY motif and thus its ubiquitination and degradation was blocked due to reduced interaction with E3 ligase SMURF1 and SMURF2. Moreover, ARHGAP5-AS1 could inhibit TGF-β signaling pathway due to its inhibitory role on SMAD7. Conclusion ARHGAP5-AS1 inhibits breast cancer cell migration via stabilization of SMAD7 protein and could serve as a novel biomarker and a potential target for breast cancer in the future.

Breast Cancer and the Renin-Angiotensin System (RAS): Therapeutic Approaches and Related Metabolic Diseases

2021 ◽  
pp. 111245
Author(s):  
Flávia Sardela de Miranda ◽  
João Pedro Tôrres Guimarães ◽  
Kalhara R. Menikdiwela ◽  
Brennan Mabry ◽  
Rabin Dhakal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metabolic Diseases ◽  
Renin Angiotensin System ◽  
Therapeutic Approaches ◽  
Angiotensin System ◽  
Renin Angiotensin

scholarly journals Progesterone promotes focal adhesion formation and migration in breast cancer cells through induction of protease-activated receptor-1

2012 ◽  
Vol 214 (2) ◽  
pp. 165-175 ◽  
Author(s):  
Jorge Diaz ◽  
Evelyn Aranda ◽  
Soledad Henriquez ◽  
Marisol Quezada ◽  
Estefanía Espinoza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Focal Adhesion ◽  
Breast Cancer Cells ◽  
Fiber Formation ◽  
Coagulation Cascade ◽  
Cancer Cell Migration

Progesterone and progestins have been demonstrated to enhance breast cancer cell migration, although the mechanisms are still not fully understood. The protease-activated receptors (PARs) are a family of membrane receptors that are activated by serine proteases in the blood coagulation cascade. PAR1 (F2R) has been reported to be involved in cancer cell migration and overexpressed in breast cancer. We herein demonstrate that PAR1 mRNA and protein are upregulated by progesterone treatment of the breast cancer cell lines ZR-75 and T47D. This regulation is dependent on the progesterone receptor (PR) but does not require PR phosphorylation at serine 294 or the PR proline-rich region mPRO. The increase in PAR1 mRNA was transient, being present at 3 h and returning to basal levels at 18 h. The addition of a PAR1-activating peptide (aPAR1) to cells treated with progesterone resulted in an increase in focal adhesion (FA) formation as measured by the cellular levels of phosphorylated FA kinase. The combined but not individual treatment of progesterone and aPAR1 also markedly increased stress fiber formation and the migratory capacity of breast cancer cells. In agreement with in vitro findings, data mining from the Oncomine platform revealed that PAR1 expression was significantly upregulated in PR-positive breast tumors. Our observation that PAR1 expression and signal transduction are modulated by progesterone provides new insight into how the progestin component in hormone therapies increases the risk of breast cancer in postmenopausal women.

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