Effects of local anesthetics on breast cancer cell viability 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.

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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

Current Cancer Therapy Reviews ◽

10.2174/1573394716999200831113335 ◽

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.

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Potential Metabolite Nymphayol Isolated from Water Lily (Nymphaea stellata) Flower Inhibits MCF-7 Human Breast Cancer Cell Growth via Upregulation of Cdkn2a, pRb2, p53 and Downregulation of PCNA mRNA Expressions

Metabolites ◽

10.3390/metabo10070280 ◽

2020 ◽

Vol 10 (7) ◽

pp. 280

Author(s):

Laila Naif Al-Harbi ◽

Pandurangan Subash-Babu ◽

Manal Abdulaziz Binobead ◽

Maha Hussain Alhussain ◽

Sahar Abdulaziz AlSedairy ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Suppressor ◽

Cell Viability ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Kinase Inhibitor ◽

B Cell Lymphoma ◽

Nuclear Antigen ◽

Mrna Levels ◽

Mcf 7

Controlled production of cyclin dependent kinases (CDK) and stabilization of tumor suppressor genes are the most important factors involved in preventing carcinogenesis. The present study aimed to explore the cyclin dependent apoptotic effect of nymphayol on breast cancer MCF-7 cells. In our previous study, we isolated the crystal from a chloroform extract of Nymphaea stellata flower petals and it was confirmed as nymphayol (17-(hexan-2-yl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-ol) using x-ray diffraction (XRD), Fourier transform infrared (FTIR), and mass spectroscopy (MS) methods. The cytotoxic effect of nymphayol on MCF-7 cells were analyzed using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The cellular and nuclear damage was determined using propidium iodide (PI) and acridine orange/ethidium bromide (AO/ErBr) staining. Tumor suppressor and apoptosis related mRNA transcript levels were determined using real-time polymerase chain reaction (RT-PCR). Nymphayol potentially inhibits MCF-7 cell viability up to 78%, and the IC50 value was observed as 2.8 µM in 24 h and 1.4 µM in 48 h. Treatment with nymphayol significantly increased reactive oxygen species (ROS) level and the tunnel assay confirmed DNA damage. We found characteristically 76% apoptotic cells and 9% necrotic cells in PI and AO/ErBr staining after 48 h treatment with 2.8 µM of nymphayol. Gene expression analysis confirmed significantly (p ≤ 0.001) increased mRNA levels of cyclin dependent kinase inhibitor 2A (Cdkn2a), retinoblastoma protein 2 (pRb2), p53, nuclear factor erythroid 2-factor 2 (Nrf2), caspase-3, and decreased B-cell lymphoma 2 (Bcl-2), murine double minute 2 (mdm2), and proliferating cell nuclear antigen (PCNA) expression after 48 h. Nymphayol effectively inhibited breast cancer cell viability, and is associated with early expression of Cdkn2a, pRb2, and activation of p53 and caspases.

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ANTICANCER ACTIVITY OF SILVER NANOPARTICLES AGAINST HUMAN BREAST CANCER CELL LINE

Kongunadu Research Journal ◽

10.26524/krj282 ◽

2019 ◽

Vol 6 (1) ◽

pp. 25-29

Author(s):

Dinesh B ◽

Ranjithkumar R ◽

Sharmila C ◽

Selvam K ◽

Chandar Shekar B

Keyword(s):

Breast Cancer ◽

Cell Viability ◽

Cell Line ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cell Line ◽

Cancer Cell Line ◽

Green Technology ◽

Future Application ◽

Dose Dependent

The present study demonstrated the effectiveness of bioinspired synthesized AgNPs against MCF-7 breast cancer cell line, we found a dramatic decrease in cell viability when the concentration of the bioinspired synthesized AgNPs was increased and there was a dose-dependent reduction in cell viability. This study further indicates the significance of green technology for nanoparticle fabrication and future application in control of several human diseases.

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Identification of a Novel TNFRSF11A (RANK) Gene Variant, Produced Through Alternative Splicing and Affecting Breast Cancer Cell Survival and Migration

Annals of Oncology ◽

10.1093/annonc/mdt086.7 ◽

2013 ◽

Vol 24 ◽

pp. iii43

Author(s):

A.D. Papanastasiou ◽

C. Sirinian ◽

M. Repanti ◽

H.P. Kalofonos

Keyword(s):

Breast Cancer ◽

Alternative Splicing ◽

Cell Survival ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Gene Variant ◽

Cancer Cell Survival ◽

And Migration ◽

Rank Gene

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HOXD3 Plays a Critical Role in Breast Cancer Stemness and Drug Resistance

Cellular Physiology and Biochemistry ◽

10.1159/000489249 ◽

2018 ◽

Vol 46 (4) ◽

pp. 1737-1747 ◽

Cited By ~ 3

Author(s):

Yue Zhang ◽

Qingyuan Zhang ◽

Zhongru Cao ◽

Yuanxi Huang ◽

Shaoqiang Cheng ◽

...

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Western Blot ◽

Cell Viability ◽

Cancer Cells ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cells ◽

Rt Pcr ◽

Integrin Β3

Background/Aims: Homeobox D3 (HOXD3) is a member of the homeobox family of genes that is known primarily for its transcriptional regulation of morphogenesis in all multicellular organisms. In this study, we sought to explore the role that HOXD3 plays in the stem-like capacity, or stemness, and drug resistance of breast cancer cells. Methods: Expression of HOXD3 in clinical breast samples were examined by RT-PCR and immunohistochemistry. HOXD3 expression in breast cancer cell lines were analyzed by RT-PCR and western blot. Ability of drug resistance in breast cancer cells were elevated by MTT cell viability and colony formation assays. We examined stemness using cell fluorescent staining, RT-PCR and western blot for stem cell marker expression. Finally, activity of wnt signaling was analyzed by FOPflash luciferase assays. RT-PCR and western blot were performed for downstream genes of wnt signaling. Results: We demonstrated that HOXD3 is overexpressed in breast cancer tissue as compared to normal breast tissue. HOXD3 overexpression enhances breast cancer cell drug resistance. Furthermore, HOXD3 upregulation in the same cell lines increased sphere formation as well as the expression levels of stem cell biomarkers, suggesting that HOXD3 does indeed increase breast cancer cell stemness. Because we had previously shown that HOXD3 expression is closely associated with integrin β3 expression in breast cancer patients, we hypothesized that HOXD3 may regulate breast cancer cell stemness and drug resistance through integrin β 3. Cell viability assays showed that integrin β 3 knockdown increased cell viability and that HOXD3 could not restore cancer cell stemness or drug resistance. Given integrin β 3’s relationship with Wnt/β-catenin signaling, we determine whether HOXD3 regulates integrin β 3 activity through Wnt/β-catenin signaling. We found that, even though HOXD3 increased the expression of Wnt/β-catenin downstream genes, it did not restore Wnt/β-catenin signaling activity, which was inhibited in integrin β3 knockdown breast cancer cells. Conclusion: We demonstrate that HOXD3 plays a critical role in breast cancer stemness and drug resistance via integrin β3-mediated Wnt/β-catenin signaling. Our findings open the possibility for improving the current standard of care for breast cancer patients by designing targeted molecular therapies that overcome the barriers of cancer cell stemness and drug resistance.

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