Abstract 32P
Background
Histone deacetylases (HDACs) play a major role in tumor progression and the development of multidrug resistance in neuroblastoma. Consequently, HDAC inhibitors (HDACis) have been introduced to induce cell cycle arrest, promote apoptosis and enhance cancer cell sensitivity to apoptotic pathways. These inhibitors increase histone acetylation, thereby activating tumor suppressor genes. Additionally, HDACis also affect non-histone proteins, such as Bax, p53, Bcl-2, and p21, facilitating apoptosis and helping to overcome resistance mechanisms in neuroblastoma.
Methods
In this study, neuroblastoma cells (SH-SY5Y) were utilized to assess the anticancer activity. Flow cytometry was used to analyse cell apoptosis following drug treatment. Confocal imaging was employed to observe morphological changes, while HDAC inhibition activity was evaluated using HDAC inhibition assay. Western blotting was conducted to determine the levels of acetylated H3 and H4 proteins, as well as the expression levels of HDAC1, HDAC2, and HDAC3 following treatment.
Results
Our findings revealed that the novel hydroxamic acid analogue effectively inhibited neuroblastoma cells, demonstrating strong anticancer activity. The compound similar effect compared to positive controls in its inhibitory effects. Western blot analysis indicated an increase in acetylation of H3 and H4 proteins without altering HDAC1, HDAC2, or HDAC3 protein levels. HDAC inhibition assay also suggesting its potential as a selective HDAC1/2 inhibitor. Nuclear staining showed noticeable nuclear bulging, indicating the activation of apoptotic pathways. This hypothesis was further supported by observed evaluated Bax protein and reduced Bcl-2 protein levels following treatment.
Conclusions
In this study, we explored the anticancer potential of a novel hydroxamic acid derivative, emphasizing the pathway involved in its inhibitory mechanism and evaluating its antitumor efficacy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Department of Biotechnology (DBT) BioCare grant [Grant ID: BT/PR20046/ BIC/101/683/2016], Government of India (GOI), India, to Dr. Babitha KS.
Disclosure
All authors have declared no conflicts of interest.