Silibinin Inhibit Cell Migration through Downregulation of RAC1 Gene Expression in Highly Metastatic Breast Cancer Cell Line

Drug Research ◽  
2020 ◽  
Vol 70 (10) ◽  
pp. 478-483
Author(s):  
Hamed Esmaeil Lashgarian ◽  
Vahid Adamii ◽  
Vajihe Ghorbanzadeh ◽  
Leila Chodari ◽  
Fayze Kamali ◽  
...  

Abstract Background Triple negative breast cancer is the most invasive breast cancer subtype and possesses poor prognosis and survival. Rho GTPase famil, especially Rac1 participates in a number of signaling events in cells with crucial roles in malignancy, migration and invasion of tumor cells. Silibinin, a flavonoid antioxidant from milk thistle has attracted attention in the recent decades for chemoprevention and chemotherapy of tumor cells. In this study, the effect of silibinin on the migration capacity of MDA-MB-231 cells, a highly metastatic human breast cancer cell line was investigated by evaluation of Rac1 expression. Method MTT wound healing and transwell assays were performed to evaluate the effects of silibinin on proliferation and migration of MDA-MB-231 cells. In addition, the influence of the silibinin on the expression of Rac1mRNAs was assessed by RT-PCR. Results Results indicated significant dose-dependent inhibitory effect of silibinin on proliferation and migration of MDA-MB-231 cells. It significantly inhibited the expression of Rac1 mRNA. Conclusion In conclusion, the results demonstrate that the silibinin can be used as an experimental therapeutic for the management of TNBC metastatic cancer.

2011 ◽  
Vol 131 (2) ◽  
pp. 276-286 ◽  
Author(s):  
Philip J. Medeiros ◽  
Baraa K. Al-Khazraji ◽  
Nicole M. Novielli ◽  
Lynne M. Postovit ◽  
Ann F. Chambers ◽  
...  

2017 ◽  
Vol 10 (5) ◽  
Author(s):  
Bahareh Zarrin ◽  
Shaghayegh Haghjooy Javanmard ◽  
Fariba Samani ◽  
Mohamadhasan Tajadini ◽  
Maryam Jamady ◽  
...  

2016 ◽  
Vol 49 (1) ◽  
Author(s):  
Kurt Buchegger ◽  
Carmen Ili ◽  
Ismael Riquelme ◽  
Pablo Letelier ◽  
Alejandro H. Corvalán ◽  
...  

2019 ◽  
Author(s):  
Dinesh Kumar ◽  
Md. Khurshidul Hassan ◽  
Niharika Pattanaik ◽  
Nachiketa Mohapatra ◽  
Manjusha Dixit

AbstractIQGAP2 is a member of IQGAPs scaffolding protein family. It has been reported as a tumor suppressor in various cancers, as well as, an oncogene in some cancers, suggesting organ specific role. Need to identify therapeutic targets which function in ER/PR independent way, prompted us to explore role of IQGAP2 in molecular mechanism in breast cancer, which was completely unknown. In vitro studies in estrogen receptor positive breast cancer cell line (MCF7) showed that low IQGAP2 expression results in increased cell proliferation, migration and invasion of cells whereas an opposite effect was observed with ectopic expression of IQGAP2. Triple negative breast cancer cell line (MDA-MB-468), with IQGAP2 depletion showed similar effect, supporting its role in ER/PR independent manner. Furthermore, we found that reduced IQGAP2 expression induces the expression of EMT markers; twist and N-cadherin and decreases the expression of MET marker, E-cadherin via the MEK/ERK pathway but not via AKT pathway. Validation of findings in patients showed a reduced IQGAP2 expression in breast cancer tissues compared to normal tissue. Patients with low levels of IQGAP2 showed correlation with higher tumor stage. Our results suggest that IQGAP2 acts as a tumor suppressor and its down regulation results in cell growth, cell invasion and EMT through the MEK/ERK signalling pathways and it hence may be a potential therapeutic target in breast cancer.


2021 ◽  
Vol 14 (11) ◽  
Author(s):  
Mohammadreza Roshanazadeh ◽  
Hossein Babaahmadi Rezaei ◽  
Mojtaba Rashidi

Background: Cancer cell metastasis is facilitated by matrix-metalloproteinases through degradation of extracellular matrix (ECM) proteins and is a major cause of mortality. One of the most common remedies for cancer is chemotherapy, which has many side effects. Therefore, it seems necessary to find a way to reduce the side effects of these drugs while maintaining their anticancer effects. Quercetin (que) is a natural substance that has been reported to have anticancer activities. Objectives: This study aims at evaluating the effect of que in combination with doxorubicin (dox) on the migration of the MDA-MB-231 breast cancer cell line. Methods: The effects of que and dox on cell viability in 24h and 48 h was assessed by MTT assay. Also, the effects of the same drugs on the cancer cells migration were evaluated, using the wound healing assay. Lastly, the effects of que and dox were assessed on the expression of MMP-2 and MMP-9 genes. Results: The combination of 50 µM of que with 32 nM of dox was selected by CI comparison. The viability and migration of cancer cells and the gelatinases genes expression were decreased after treatment with individual drugs. The migration and the expression of MMP-2 and MMP-9 genes after treatment with the combination of que and dox was significantly reduced compared to the treatment with que and dox alone. Conclusions: Que inhibits the viability and migration of MDA-MB-231 cancer cells and synergistically enhances the effects of dox on the survival and migration of these cells. Hence, we propose this drug combination as a path for further research on breast cancer therapy.


2020 ◽  
Vol 21 (5) ◽  
Author(s):  
Soudabeh Kavousipour ◽  
Pooneh Mokarram ◽  
Mahdi Barazesh ◽  
Elham Arabizadeh ◽  
Vahid Razban ◽  
...  

Background: The intracellular signaling pathways stimulated by CD44/hyaluronic acid (HA) interaction play a central role in the invasion and migration of cancer cells. Epithelial-mesenchyme transition (EMT) is an important factor in cancer metastasis and migration, which can be stimulated by the snail transcription factor. Previous studies showed cells that were subjected to snail-induced EMT, characterized by a CD44high/CD24low phenotype, expressed at their surface. Objectives: The aim of this study was to assess the inhibitory effect of CD44/HA interaction on the snail expression and invasive behavior of aggressive breast cancer cell line with a high CD44 expression in 2D and 3D culture. The cell surface binding capacity of the selected aptamer was evaluated via flow cytometry assay. Methods: To test our hypothesis, we disrupted the CD44/HA interaction by DNA aptamer, which specifically binds to the Hyaluronic Acid Binding Domain (HABD) of CD44. Then, expression level of snail mRNA was evaluated in MDA-MB 231 cells, cultured in 2D and 3D conditions by real-time PCR. Furthermore, invasive behavior was evaluated, using wound healing assay. Results: The results of this study showed that CD44 aptamer reduced snail expression and invasive behavior in MDA-MB 231 cell line. In addition, our result indicated that cells cultured in 3D were more sensitive to the aptamer in comparison to those cultured in the 2D model. Conclusions: The inhibition of CD44-HA interaction, using aptamer, negatively regulates the CD44 function in aggressive breast cancer cell line with the high level of CD44 expression.


Biology ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 16 ◽  
Author(s):  
Mª Carmen Ocaña ◽  
Beatriz Martínez-Poveda ◽  
Ana R. Quesada ◽  
Miguel Ángel Medina

Metabolic reprogramming in tumor cells is considered one of the hallmarks of cancer. Many studies have been carried out in order to elucidate the effects of tumor cell metabolism on invasion and tumor progression. However, little is known about the immediate substrate preference in tumor cells. In this work, we wanted to study this short-time preference using the highly invasive, hormone independent breast cancer cell line MDA-MB-231. By means of Seahorse and uptake experiments, our results point to a preference for glucose. However, although both glucose and glutamine are required for tumor cell proliferation, MDA-MB-231 cells can survive two days in the absence of glucose, but not in the absence of glutamine. On the other hand, the presence of glucose increased palmitate uptake in this cell line, which accumulates in the cytosol instead of going to the plasma membrane. In order to exert this effect, glucose needs to be converted to glycerol-3 phosphate, leading to palmitate metabolism through lipid synthesis, most likely to the synthesis of triacylglycerides. The effect of glucose on the palmitate uptake was also found in other triple-negative, invasive breast cancer cell lines, but not in the non-invasive ones. The results presented in this work suggest an important and specific role of glucose in lipid biosynthesis in triple-negative breast cancer.


2018 ◽  
Vol Volume 10 ◽  
pp. 535-544 ◽  
Author(s):  
Juan Zhou ◽  
Wen-Wen Zhang ◽  
Fang Peng ◽  
Jia-Yuan Sun ◽  
Zhen-Yu He ◽  
...  

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