Complex molecular mechanisms cooperate to mediate histone deacetylase inhibitors anti-tumour activity in neuroblastoma cells

Abstract

Background: Histone deacetylase inhibitors (HDACi) are a new class of promising anti-tumour agent inhibiting cell proliferation and survival in tumour cells with very low toxicity toward normal cells. Neuroblastoma (NB) is the second most common solid tumour in children still associated with poor outcome in higher stages and, thus NB strongly requires novel treatment modalities.

Epigenetic Silencing of the Tumor Suppressor MicroRNAHsa-miR-124aRegulates CDK6 Expression and Confers a Poor Prognosis in Acute Lymphoblastic Leukemia

“…4B), in contrast to up-regulation of hsa-miR-124a, which did not induce apoptosis. This effect probably is due to the fact that sodium butyrate is not a specific inhibitor of CDK6 but can also inhibit other pathways involved in cell cycle and apoptosis, such as p53, cyclin D1, or histone deacetylase (27,28). Figure 5.…”

Inhibition of Sirtuin 6 Induces Neuroblastoma Differentiation

“…13-Cis RA is administered in children with NB who have minimal residual disease following myeloablative chemotherapy and autologous stem cell transplantation (4). Histone deacetalyase inhibitors have also shown preclinical efficacy in NB models (22,23). In fact, histone deacetalyase inhibitors have been shown to have synergistic effects with RA in eliciting NB differentiation (23,24).…”

Discovery of N-hydroxy-4-(3-phenylpropanamido)benzamide derivative 5j, a novel histone deacetylase inhibitor, as a potential therapeutic agent for human breast cancer

“…3), SAHA was used as a positive control. In MDA-MB-231 cells, 5j mainly induced G 1 phase , 16,17 since 5j exhibited similar cell cycle and apoptosis effects on MDA-MB-231 and MCF-7 cells to SAHA, here we mainly examined the effects of 5j on the expression of p21, Bcl-x L , Caspase 3 and so on. p21 is CDK inhibitor which involved in cell cycle regulation and apoptosis.…”

“…Therefore, 5j induced apoptosis may be also dependent on the Bcl-2/Bcl-x L pathway. HDAC inhibitors induce caspases-dependent cell death in some cell lines and apoptosis occurs following cell cycle arrest in G 2 /M phase, 17 Caspase 3, an effector caspase, belongs to Caspases family, a unique family of cysteine proteases, execute programmed cell death, 20 and essential for DNA fragmentation and some of the morphological changes associated with apoptosis. 21 As shown in (Fig.…”

“…HDAC inhibitors induce caspases-dependent cell death in some cell lines and apoptosis which occurs following cell cycle arrest in G 2 /M phase, 17 and the molecular mechanism of SAHA …”