Through the SNAIL transcription factors ( 16- 18). Several types of CRC, is involved in aberrant HDAC expression Transition (EMT) process, which plays a role in the growth of Upregulation pf HDAC1/2 found at the beginning of colonĬarcinogenesis is implicated in cell tumorigenicity via chromatin In CRC cells, several studies have revealed that the Therefore, the inhibition of HDAC1/2 has emerged Upregulation of HDAC1/2 is involved in the progression of various The expression of CDK inhibitors, which leads to a cell cycle block (CDK) inhibitor p21, a key component in cell cycle control andĪpoptosis ( 10- 12). Suppressor p53 in the regulation of the cyclin-dependent kinase The effects of HDACs on cell behavior were recentlyĭemonstrated in several studies. Remodeling and deacetylation (NuRD) and co-repressor forĮlement-1-silencing transcription factor (CoREST) ( 8, 9). Stable, multiprotein co-repressor complexes: Sin3, nucleosome I, are found in mammalian cell nuclei and are located in 3 major, The 18 isoforms of this family are classified intoĤ groups: The zinc-dependent HDACs comprise class I (HDAC1, 2, 3Īnd 8), class II (HDAC4, 5, 6, 7, 9 and 10) and class IV (HDAC 11),Īnd the NAD +-dependent HDACs which belong to class III Histone deacetylases (HDACs) are a family of crucialĮpigenetic enzymes that play an important role in the regulation of Such alterations are commonly perceived to be good molecular
Including familial history, inherited genetic mutations and foodĮpigenetic alteration, can drive the transformation from normal Several risk factors are associated with the development of CRC, Mortality, accounting for approximately 1.36 million new cases andĦ94,000 deaths worldwide in 2012 ( 1, 2). Malignancy and the fourth highest cause of cancer-related Thus, CBUD‑1001 may prove to be a promising novel drug candidate for CRC therapy.Ĭolorectal cancer (CRC) is the third most common Of note, it was found that CBUD‑1001 attenuates the cell motility of CRC cells by downregulating the EMT signaling pathway.
Further investigation using CRC cells demonstrated that CBUD‑1001 inhibited HDAC activity by hyper‑acetylating histones H3 and H4, and it exerted an apoptotic effect by activating a mitochondrial‑dependent pathway. Molecular docking analysis rationalized the high potency of CBUD‑1001 by validating its conformation in the HDAC active site. CBUD‑1001 exerted a potent inhibitory effect on HDAC enzyme activity and exhibited anticancer potency against CRC cell lines. A novel fluorinated aminophenyl‑benzamide‑based compound, CBUD‑1001, was designed to specifically target HDAC1, and it was then synthesized and evaluated. The aim of the present study was to discover a novel, potent HDAC inhibitor and demonstrate its anticancer effect and molecular mechanisms in CRC cells. Some HDAC inhibitors have been shown to be efficient agents for cancer treatment. Histone deacetylases (HDACs) are a class of enzymes responsible for the epigenetic regulation of gene expression. Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies and is a leading cause of cancer‑related mortality worldwide.