Article

Epigenetic therapy for breast cancer.

Laboratory for Gynecological Oncology, Department of Biomedicine, Women's Hospital, University of Basel, Hebelstrasse 20, Room 420, Basel, CH 4031, Switzerland; E-Mails: (F.-F.C.); (C.K.); (B.Z.); (W.-J.C.).
International Journal of Molecular Sciences (Impact Factor: 2.46). 01/2011; 12(7):4465-87. DOI: 10.3390/ijms12074465
Source: PubMed

ABSTRACT Both genetic and epigenetic alterations can control the progression of cancer. Genetic alterations are impossible to reverse, while epigenetic alterations are reversible. This advantage suggests that epigenetic modifications should be preferred in therapy applications. DNA methyltransferases and histone deacetylases have become the primary targets for studies in epigenetic therapy. Some DNA methylation inhibitors and histone deacetylation inhibitors are approved by the US Food and Drug Administration as anti-cancer drugs. Therefore, the uses of epigenetic targets are believed to have great potential as a lasting favorable approach in treating breast cancer.

0 Bookmarks
 · 
131 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mammalian sterile 20-like kinase 1 (Mst1) has been proved in the process of apoptosis and tumor suppression. The aim of the study was to investigate the expression of Mst1 in breast cancer and to evaluate its prognostic significance. The expression of Mst1 was examined in 110 breast cancer patients by immunohistochemistry, in which 80 (72.7 %) were defined as positive for Mst1 expression. Patients with negative expression of Mst1 had poor overall survival, comparing with those with positive expression using Kaplan-Meier survival analysis (P = 0.009). Multivariate analysis using Cox proportional hazards model showed that Mst1 expression was a significant independent prognostic factor in breast cancer (P = 0.030). Our results presented the tumor suppressive role of Mst1, and confirmed Mst1 was a prognostic factor in human breast cancer.
    Tumor Biology 06/2013; · 2.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Thymus (T.) serpyllum (wild thyme) is an aromatic medicinal plant due to its several biological properties, including anticancer activity. Breast cancer is one of the most common malignancies and increasing evidence supports that it is not only a genetic but also an epigenetic disease. Epigenetics investigates changes in gene expression caused by mechanisms that do not involve alterations in DNA sequence. DNA methylation and histone acetylation are the most widely studied epigenetic changes in cancer cells. This study evaluated the effects of T. serpyllum on apoptosis and epigenetic events in breast cancer cells. XTT cell viability assay was used to determine cytotoxicity. DNA fragmentation and caspase 3/7 activity assays were used in the assesment of apoptosis. DNA methyltransferase (DNMT) and histone deacetylase (HDAC) activities were evaluated by ELISA and verified by qRT-PCR. T. serpyllum extract induced significant cytotoxicity in breast cancer cells (MCF-7 and MDA-MB-231) but not in normal cells. It also induced apoptosis and inhibited the DNMT and HDAC activities in MDA-MB-231 cells. In the present study, the first preliminary data on the effects of the methanolic extract of T. serpyllum in normal and breast cancer cells were obtained and suggest that T. serpyllum may be a promising candidate in the development of novel therapeutic drugs for breast cancer treatment.
    Nutrition and Cancer 11/2012; 64(8):1245-50. · 2.70 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BRCA1 and BRCA2 genes are crucial for double-strand break repair by homologous recombination, and mutations in these genes are responsible for most familial breast carcinomas. Cells with inactivating mutations of the BRCA1 or BRCA2 tumor suppressor genes are sensitive to poly (ADP-ribose) polymerase-1 (PARP1) inhibitors. Already in 2010, it has been predicted, that BRCA1 hypermethylation might be sensitive to PARP1 inhibitor. However, till today, a statistically significant proof has been missing, and the effectiveness of PARP1 inhibitors for breast cancer caused by BRCA1 promoter hypermethylation remained elusive. Pyrosequencing has been proposed as an optimal method to investigate the methylation status of the BRCA1 genes. Here, we show for the first time that BRCA1 CpG island hypermethylation is sensitive to PARP1 inhibitors. In clinical settings, this might improve treatment response and provide a more personalized therapy for breast cancer patients. Furthermore, the determination of methylation status of BRCA1 and other genes of the BRCA/homologous recombination (HR) pathway may be an important predictive classifier of response to PARP inhibitor therapy.
    Tumor Biology 12/2013; · 2.52 Impact Factor

Full-text

View
1 Download
Available from