Vorinostat (SAHA), an inhibitor of class I and II of histone deacetylases, is the first histone deacetylase inhibitor (HDI) approved for the treatment of cutaneous T-cell lymphoma in 2006. HDIs are promising anticancer agents that inhibit the proliferation of many types of cancer cells including breast carcinoma (BC). BC is a heterogeneous disease with variable biological behavior, morphological features, and response to therapy. Although significant progress in the treatment of BC has been made, high toxicity to normal cells, serious side effects, and the occurrence of multi-drug resistance limit the effective therapy of BC patients. Therefore, new active agents which improve the effectiveness of currently used regimens are highly needed. This manuscript analyzes preclinical and clinical trials data of SAHA, applied individually or in combination with other anticancer agents, considering different histological subtypes of BC.

Histone deacetylase inhibitors (HDIs) are a group of potent epigenetic drugs which have been investigated for their therapeutic potential in various clinical disorders, including hematological malignancies and solid tumors. Currently, several HDIs are already in clinical use and many more are on clinical trials. HDIs have shown efficacy to inhibit initiation and progression of cancer cells. Nevertheless, both pro-invasive and anti-invasive activities of HDIs have been reported, questioning their impact in carcinogenesis. The aim of this review is to compile and discuss the most recent findings on the effect of HDIs on the epithelial-mesenchymal transition (EMT) process in human cancers. We have summarized the impact of HDIs on epithelial (E-cadherin, β-catenin) and mesenchymal (N-cadherin, vimentin) markers, EMT activators (TWIST, SNAIL, SLUG, SMAD, ZEB), as well as morphology, migration and invasion potential of cancer cells. We further discuss the use of HDIs as monotherapy or in combination with existing or novel anti-neoplastic drugs in relation to changes in EMT.

Valproic acid (2-propylpentanoic acid, VPA) is a short-chain fatty acid, a member of the group of histone deacetylase inhibitors (HDIs). VPA has been successfully used in the treatment of epilepsy, bipolar disorders, and schizophrenia for over 50 years. Numerous in vitro and in vivo pre-clinical studies suggest that this well-known anticonvulsant drug significantly inhibits cancer cell proliferation by modulating multiple signaling pathways. Breast cancer (BC) is the most common malignancy affecting women worldwide. Despite significant progress in the treatment of BC, serious adverse effects, high toxicity to normal cells, and the occurrence of multi-drug resistance (MDR) still limit the effective therapy of BC patients. Thus, new agents which improve the effectiveness of currently used methods, decrease the emergence of MDR, and increase disease-free survival are highly needed. This review focuses on in vitro and in vivo experimental data on VPA, applied individually or in combination with other anti-cancer agents, in the treatment of different histological subtypes of BC.

The review collects together some recent information on the identity and pharmacological properties of magnoflorine, a quaternary aporphine alkaloid, that is widely distributed within the representatives of several botanical families like Berberidaceae, Magnoliaceae, Papaveraceae, or Menispermaceae. Several findings published in the scientific publications mention its application in the treatment of a wide spectrum of diseases including inflammatory ones, allergies, hypertension, osteoporosis, bacterial, viral and fungal infections, and some civilization diseases like cancer, obesity, diabetes, dementia, or depression. The pharmacokinetics and perspectives on its introduction to therapeutic strategies will also be discussed.

Histone deacetylase inhibitors (HDIs) are promising anticancer drugs, which inhibit proliferation of a wide variety of cancer cells including breast carcinoma cells. In the present study, we investigated the influence of valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), alone or in combination with cisplatin (CDDP) on proliferation, induction of apoptosis and cell cycle progression in MCF7, T47D and MDA-MB-231 human breast carcinoma cell lines. The type of interaction between HDIs and CDDP was determined by an isobolographic analysis. The isobolographic analysis is a very precise and rigorous pharmacodynamic method, to determine the presence of synergism, addition or antagonism between different drugs with using variety of fixed dose ratios. Our experiments show that the combinations of CDDP with SAHA or VPA at a fixed-ratio of 1:1 exerted additive interaction in the viability of MCF7 cells, while in T47D cells there was a tendency to synergy. In contrast, sub-additive (antagonistic) interaction was observed for the combination of CDDP with VPA in MDA-MB-231 “triple-negative” (i.e. estrogen receptor negative, progesterone receptor negative, and HER-2 negative) human breast cancer cells, whereas combination of CDDP with SAHA in the same MDA-MB-231 cell line yielded additive interaction. Additionally, combined HDIs/CDDP treatment resulted in increase in apoptosis and cell cycle arrest in all tested breast cancer cell lines in comparison with a single therapy. In conclusion, the additive interaction of CDDP with SAHA or VPA suggests that HDIs could be combined with CDDP in order to optimize treatment regimen in some human breast cancers.

Acetylation and deacetylation are posttranslational modifications (PTMs) which affect the regulation of chromatin structure and its remodeling. Acetylation of histone 3 at lysine placed on position 18 (H3K18Ac) plays an important role in driving progression of many types of cancer, including breast, colon, lung, hepatocellular, pancreatic, prostate, and thyroid cancer. The aim of this review is to analyze and discuss the newest findings regarding the role of H3K18Ac and acetylation of other histones in carcinogenesis. We summarize the level of H3K18Ac in different cancer cell lines and analyze its association with patients’ outcomes, including overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS). Finally, we describe future perspectives of cancer therapeutic strategies based on H3K18 modifications.