scholarly journals Effect of Helix aspersa extract on TNFα, NF-κB and some tumor suppressor genes in breast cancer cell line Hs578T

2017 ◽  
Vol 13 (50) ◽  
pp. 281 ◽  
Author(s):  
Ibtissem El Ouar ◽  
Cornelia Braicu ◽  
Dalila Naimi ◽  
Alexendru Irimie ◽  
Ioana Berindan-Neagoe
Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769225 ◽  
Author(s):  
Umesh Kumar ◽  
Ujjawal Sharma ◽  
Garima Rathi

One of the mechanisms for epigenetic silencing of tumor suppressor genes is hypermethylation of cytosine residue at CpG islands at their promoter region that contributes to malignant progression of tumor. Therefore, activation of tumor suppressor genes that have been silenced by promoter methylation is considered to be very attractive molecular target for cancer therapy. Epigenetic silencing of glutathione S-transferase pi 1, a tumor suppressor gene, is involved in various types of cancers including breast cancer. Epigenetic silencing of tumor suppressor genes can be reversed by several molecules including natural compounds such as polyphenols that can act as a hypomethylating agent. Curcumin has been found to specifically target various tumor suppressor genes and alter their expression. To check the effect of curcumin on the methylation pattern of glutathione S-transferase pi 1 gene in MCF-7 breast cancer cell line in dose-dependent manner. To check the reversal of methylation pattern of hypermethylated glutathione S-transferase pi 1, MCF-7 breast cancer cell line was treated with different concentrations of curcumin for different time periods. DNA and proteins of treated and untreated cell lines were isolated, and methylation status of the promoter region of glutathione S-transferase pi 1 was analyzed using methylation-specific polymerase chain reaction assay, and expression of this gene was analyzed by immunoblotting using specific antibodies against glutathione S-transferase pi 1. A very low and a nontoxic concentration (10 µM) of curcumin treatment was able to reverse the hypermethylation and led to reactivation of glutathione S-transferase pi 1 protein expression in MCF-7 cells after 72 h of treatment, although the IC50 value of curcumin was found to be at 20 µM. However, curcumin less than 3 µM of curcumin could not alter the promoter methylation pattern of glutathione S-transferase pi 1. Treatment of breast cancer MCF-7 cells with curcumin causes complete reversal of glutathione S-transferase pi 1 promoter hypermethylation and leads to re-expression of glutathione S-transferase pi 1, suggesting it to be an excellent nontoxic hypomethylating agent.


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 08 ◽  
Author(s):  
Alireza Pooyae Golizadeh ◽  
Asa Ebrahimi ◽  
Mahdi Rahaie ◽  
Farzaneh Samiee

Background: By considering [6]-gingerol as an important polyphenol, ginger has been identified to be related to cancer. Objective: In this study, the evaluation of ginger extract on the expressions of four genes from different categories involved in breast cancer process in Balb/C mouse after 14 days was the main objective. Methods: In term of this research, ethanol extraction methods for extracting ginger rhizomes with the goal of increasing [6]-gingerol were used. In this regard, MTT test was accomplished for whole ginger extract to confirm its effect on 4T1 breast cancer cell line (murine mammary carcinoma cell). Afterward, the transplanted breast cancer Balb/C mouse was used to be treated by whole ginger extract (0.02 g/kg of mouse weight). The expressions of STAT3, β-catenin, P53, APC, genes were evaluated, after 14-day treatment. Results: The results showed that 70% ethanol and microwave extraction method can be considered as the best method for extracting ginger extract. The results of the expression of β-catenin has decreased in blood and liver of the treated group. Moreover, the expression of STAT3 oncogenes has significantly decreased in the liver tissue. In addition, the expressions of APC suppressor genes have increased in Blood and liver. Conclusion: In conclusion, treatment by 0.02 g/kg of mouse weight of ginger extract after 14 days increased the expressions of APC as suppressor genes and β-catenin oncogene in Blood and liver of the breast cancer group.


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