Histone deacetylases modulate resistance to the therapy in lung cancer

Abstract

The acetylation status of histones located in both oncogenes and tumor suppressor genes modulate cancer hallmarks. In lung cancer, changes in the acetylation status are associated with increased cell proliferation, tumor growth, migration, invasion, and metastasis. Histone deacetylases (HDACs) are a group of enzymes that take part in the elimination of acetyl groups from histones. Thus, HDACs regulate the acetylation status of histones. Although several therapies are available to treat lung cancer, many of these fail because of the development of tumor resistance. One mechanism of tumor resistance is the aberrant expression of HDACs. Specific anti-cancer therapies modulate HDACs expression, resulting in chromatin remodeling and epigenetic modification of the expression of a variety of genes. Thus, HDACs are promising therapeutic targets to improve the response to anti-cancer treatments. Besides, natural compounds such as phytochemicals have potent antioxidant and chemopreventive activities. Some of these compounds modulate the deregulated activity of HDACs (e.g. curcumin, apigenin, EGCG, resveratrol, and quercetin). These phytochemicals have been shown to inhibit some of the cancer hallmarks through HDAC modulation. The present review discusses the epigenetic mechanisms by which HDACs contribute to carcinogenesis and resistance of lung cancer cells to anticancer therapies.

POxload: Machine Learning Estimates Drug Loadings of Polymeric Micelles

“…This includes, for example, ladarixin (CXCR1/2 inhibitor) and resminostat (HDAC-6 inhibitor). Both classes of drugs are investigated for synergistic effects with other anticancer agents, including taxanes, , and are considered, e.g., for combination therapies against pancreatic cancer. , IOWH-032 is a CFTR inhibitor that also suppresses SARS-CoV-2 replication and GS-6620 is a precursor of the antiviral drug remdesivir and assessed as treatment against the Ebola virus . These compounds might be tested in future experimental studies to extend the available data for QSPR modeling and establish pOx/pOzi-based DDS for more therapeutic fields.…”

Sodium butyrate supresses malignant human mast cell proliferation, downregulates expression of KIT and promotes differentiation

“…2 Percent of cells that were trypan blue negative. 3 Ratio of C-KIT expression of cells treated with 1000 µM NaBu for 3 days, compared to untreated cells. 4 Ratio of C-KIT expression of cells treated with 100 µM NaBu for 4 days, compared to untreated cells.…”

“…HDACs, also called lysine deacetylases (KDAC), catalyze the removal of acetyl groups from ϵ-N-acetyl lysine amino acid on a histone or non-histone proteins, causing changes in chromatic structure and thus gene expression (2). HDACs modulate the expression of multiple proteins involved in cancer initiation and progression and may play a role in resistance to chemotherapy (3,4). Mutation and/or aberrant expression of HDACs is often observed in numerous human cancers, making them anti-cancer therapeutic targets (4).…”

Water-soluble 4-(dimethylaminomethyl)heliomycin exerts greater antitumor effects than parental heliomycin by targeting the tNOX-SIRT1 axis and apoptosis in oral cancer cells

“…Heliomycin (also called resistomycin) was originally isolated from marine sponges and shown to possess a wide range of activities, including HDAC inhibitor activity [10]. HDAC inhibitors are currently under investigation for playing important roles in cancer epigenetic pathways, exhibiting antitumor activity, and decreasing tumor resistance [53][54][55]. Our group has explored the anticancer properties of heliomycin and established its binding with SIRT1 in the native cellular environment of bladder cancer cells [25,26].…”