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 Stransferase pi 1 protein expression in MCF-7 cells after 72 h of treatment, although the IC 50 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.
Breast cancer is a carcinoma of mammary glands, which starts off as abnormal proliferation of ductal cells. This could, then, become either benign tumours or metastatic carcinomas. It is one of the most common causes of deaths because of cancer, and is one of the most common types of cancer in women in the whole world. India along with the US and China accounts for one-third of the breast cancer burden. The breast cancer carcinogenesis is attributed to epigenetics, which is the study of the reversible changes in the phenotype without any change in the DNA sequence. Genes, which are concerned with proliferation, anti-apoptosis, invasion, and metastasis, have been seen undergoing epigenetic changes in breast cancer. Cancer can be caused either by global hypomethylation (causing activation of oncogenes and leading to chromosomal instability) or by locus-specific hypermethylation (causing repression of gene expression and genetic instability due to inactivation of DNA repair genes). Other epigenetic mechanisms involved in carcinogenesis are histone modification and nucleosomal remodeling.
Breast cancer is a carcinoma of mammary glands, which starts off as abnormal proliferation of ductal cells. This could, then, become either benign tumours or metastatic carcinomas. It is one of the most common causes of deaths because of cancer, and is one of the most common types of cancer in women in the whole world. India along with the US and China accounts for one-third of the breast cancer burden. The breast cancer carcinogenesis is attributed to epigenetics, which is the study of the reversible changes in the phenotype without any change in the DNA sequence. Genes, which are concerned with proliferation, anti-apoptosis, invasion, and metastasis, have been seen undergoing epigenetic changes in breast cancer. Cancer can be caused either by global hypomethylation (causing activation of oncogenes and leading to chromosomal instability) or by locus-specific hypermethylation (causing repression of gene expression and genetic instability due to inactivation of DNA repair genes). Other epigenetic mechanisms involved in carcinogenesis are histone modification and nucleosomal remodeling.
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