Down regulation of Pinkbar/pAKT and MMP2/MMP9 expression in MDA-MB-231 breast cancer cells as potential targets in cancer therapy by hAMSCs secretome

2021 ◽  
Author(s):  
Termeh Shakery ◽  
Fatemeh Safari
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Growth Factor Receptor ◽  
3D Cell Culture ◽  
Therapeutic Effects ◽  
Down Regulation ◽  
Egfr Signaling Pathway

Breast cancer (BC) is one of the most causes of cancer-related death among women worldwide. Cancer therapy based on stem cells was considered as a novel and promising platform. In present study, we explored the therapeutic effects of human amniotic mesenchymal stromal cells (hAMSCs) through Pinkbar (planar intestinal-and kidney-specific BAR domain protein), pAKT, and matrix metalloproteinases including MMP2, MMP9 on MDA-MB-231 breast cancer cells. To do so, we employed a co-culture system using 6 well plates transwell with a diameter of 0.4 μm pore sized. After 72h hAMSCs-treated MDA-MB-231 breast cancer cells, the expression of Epidermal growth factor receptor (EGFR), and c-Src (a key mediator in EGFR signaling pathway), Pinkbar, pAKT, MMP2, and MMP9 was analyzed by using quantitative real time PCR (qRT-PCR) and western blot methods. Based on using 2D and 3D cell culture models, the significant reduction of tumor cell growth and motility through down regulation of EGFR, c-Src, Pinkbar, pAKT, MMP2, and MMP9 in MDA-MB-231 breast cancer cells was shown. Also, the induction of cellular apoptosis also found. Our finding indicates that the hAMSCS secretome has therapeutic effects on cancer cells. To identify the details of the molecular mechanisms, more experiments will be required.

Alkylamino Phenol Derivative Induces Apoptosis by Inhibiting EGFR Signaling Pathway in Breast Cancer Cells

2020 ◽  
Vol 20 (7) ◽  
pp. 809-819 ◽  
Author(s):  
Suresh Palanivel ◽  
Olli Yli-Harja ◽  
Meenakshisundaram Kandhavelu
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Breast Cancer Cells ◽  
Growth Factor Receptor ◽  
Annexin V ◽  
Binding Mode ◽  
Quantitative Structure Activity Relationship ◽  
Phenol Derivative ◽  
Egfr Signaling Pathway

Background and Objective: The present study was carried out to evaluate the anticancer property of an alkylamino phenol derivative -2-((3,4-Dihydroquinolin-1(2H)-yl)(p-tolyl)methyl)phenol) (THTMP) against human breast cancer cells. The cytotoxicity of the THTMP was assessed to know its specificity towards breast cancer cells without affecting the normal cells. Methods: The THTMP was synthesized and the cytotoxicity was assessed by MTT assay, Caspases enzyme activity, DNA fragmentation and FITC/Annexin V, AO/EtBr staining, RT-PCR and QSAR. In addition, ADME analysis was executed to understand the mode of action of THTMP. Results: THTMP showed potential cytotoxic activity against the growth of MCF7 and SK-BR3 cells with the IC50 values of 87.92μM and 172.51μM, respectively. Interestingly, THTMP found to activate caspase 3 and caspase 9 enzymes in cancer cells, which are the key enzymes implicated in apoptosis. THTMP induced apoptosis in which 33% of the cells entered the late apoptotic stage after 24h of treatment. The results also revealed that the apoptotic response could be influenced by the association of THTMP with the Epidermal Growth Factor Receptor (EGFR) mediated inhibition of the Phosphatidylinositol 3-Kinase (PI3K)/S6K1 signaling pathway. In addition, docking was performed to study the binding mode of the THTMP, which shows better interaction with EGFR. The structural elucidation of THTMP by Quantitative Structure-Activity Relationship model (QSAR) and ADMET screening suggested, THTMP as an effective anticancer compound. Conclusion: This work strengthens the potential of a promising drug-like compound, THTMP, for the discovery of anticancer drug against breast cancer.

Lobetyolin inhibits the proliferation of breast cancer cells via ASCT2 down-regulation-induced apoptosis

2021 ◽  
pp. 096032712110214
Author(s):  
Yansong Chen ◽  
Ye Tian ◽  
Gongsheng Jin ◽  
Zhen Cui ◽  
Wei Guo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Glutamine Metabolism ◽  
Down Regulation ◽  
Anti Cancer ◽  
Induced Apoptosis ◽  
Glutamine Uptake

This study aimed to investigate the anti-cancer effect of lobetyolin on breast cancer cells. Lobetyolin was incubated with MDA-MB-231 and MDA-MB-468 breast cancer cells for 24 h. Glucose uptake and the mRNA expression of GLUT4 ( SLC2A4), HK2 and PKM2 were detected to assess the effect of lobetyolin on glucose metabolism. Glutamine uptake and the mRNA expression of ASCT2 ( SLC1A5), GLS1, GDH and GLUL were measured to assess the effect of lobetyolin on glutamine metabolism. Annexin V/PI double staining and Hoechst 33342 staining were used to investigate the effect of lobetyolin on cell apoptosis. Immunoblot was employed to estimate the effect of lobetyolin on the expression of proliferation-related markers and apoptosis-related markers. SLC1A5 knockdown with specific siRNA was performed to study the role of ASCT2 played in the anti-cancer effect of lobetyolin on MDA-MB-231 and MDA-MB-468 breast cancer cells. C-MYC knockdown with specific siRNA was performed to study the role of c-Myc played in lobetyolin-induced ASCT2 down-regulation. Myr-AKT overexpression was performed to investigate the role of AKT/GSK3β signaling played in lobetyolin-induced down-regulation of c-Myc and ASCT2. The results showed that lobetyolin inhibited the proliferation of both MDA-MB-231 and MDA-MB-468 breast cancer cells. Lobetyolin disrupted glutamine uptake via down-regulating ASCT2. SLC1A5 knockdown attenuated the anti-cancer effect of lobetyolin. C-MYC knockdown attenuated lobetyolin-caused down-regulation of ASCT2 and Myr-AKT overexpression reversed lobetyolin-caused down-regulation of both c-Myc and ASCT2. In conclusion, the present work suggested that lobetyolin exerted anti-cancer effect via ASCT2 down-regulation-induced apoptosis in breast cancer cells.

scholarly journals Facile fabricating of rGO and Au/rGO nanocomposites using Brassica oleracea var. gongylodes biomass for non-invasive approach in cancer therapy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fatemeh Yousefimehr ◽  
Saeed Jafarirad ◽  
Roya Salehi ◽  
Mohammad Sadegh Zakerhamidi
Keyword(s):  
Breast Cancer ◽  
Green Synthesis ◽  
Cancer Cells ◽  
Brassica Oleracea ◽  
Photothermal Therapy ◽  
Breast Cancer Cells ◽  
Near Infrared ◽  
Therapeutic Effects ◽  
Invasive Approach ◽  
Au Nps

AbstractIn this study, we report a facile green-synthesis route for the fabrication of reduced graphene oxide (rGO) using biomass of Brassica oleracea var. gongylodes (B. oleracea). In addition, we have attempted to provide a green synthesis approach to prepare Gold nanoparticles (Au NPs) on the surface of rGO by using stem extract of B. oleracea. The synthesized Au/rGO nanocomposite was evaluated using UV–visible and FTIR spectroscopy, XRD, Raman, FE-SEM, EDX, AFM and DLS techniques. The obtained results demonstrated that the synthesized Au NPs on the surface of rGO was spherical with sizes ranging about 12–18 nm. The Au/rGO NC was, also, developed as photo-synthesizer system for the photothermal therapy (PTT) of MCF7 breast cancer cells. The near-infrared (NIR) photothermal properties of Au/rGO NCs was evaluated using a continuous laser at 808 nm with power densities of 1 W.cm−2. Their photothermal efficacy on MCF7 breast cancer cells after optimizing the proper concentration of the NCs were evaluated by MTT assay, Cell cycle and DAPI staining. In addition, the potential of the synthesized Au/rGO NCs on reactive oxygen species generating and antioxidant activity were assessed by DPPH. Au/rGO NCs possess high capacity to light-to-heat conversion for absorption in range NIR light, and it is able to therapeutic effects on MCF7 cells at a low concentration. The maximum amount of cell death is 40.12% which was observed in treatment groups that received a combination of Au/rGO NCs and laser irradiation. The results demonstrate that the nanomaterials synthesized by green approach lead to efficient destruction of cancer cell and might thus serve as an excellent theranostic agent in Photothermal therapy applications.

scholarly journals Pharmacodynamic Markers for Choline Kinase Down-regulation in Breast Cancer Cells

Neoplasia ◽  
2009 ◽  
Vol 11 (5) ◽  
pp. 477-484 ◽  
Author(s):  
Sridhar Nimmagadda ◽  
Kristine Glunde ◽  
Martin G. Pomper ◽  
Zaver M. Bhujwalla
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Choline Kinase ◽  
Down Regulation ◽  
Pharmacodynamic Markers
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