A novel HDAC1 inhibitor, CBUD‑1001, exerts anticancer effects by modulating the apoptosis and EMT of colorectal cancer cells

  • Authors:
    • Se Lim Kim
    • Minh Thanh La
    • Min Woo Shin
    • Sang‑Wook Kim
    • Hee‑Kwon Kim
  • View Affiliations

  • Published online on: August 10, 2020     https://doi.org/10.3892/ijo.2020.5109
  • Pages: 1027-1038
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies and is a leading cause of cancer‑related mortality worldwide. Histone deacetylases (HDACs) are a class of enzymes responsible for the epigenetic regulation of gene expression. Some HDAC inhibitors have been shown to be efficient agents for cancer treatment. 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. A novel fluorinated aminophenyl‑benzamide‑based compound, CBUD‑1001, was designed to specifically target HDAC1, and it was then synthesized and evaluated. CBUD‑1001 exerted a potent inhibitory effect on HDAC enzyme activity and exhibited anticancer potency against CRC cell lines. Molecular docking analysis rationalized the high potency of CBUD‑1001 by validating its conformation in the HDAC active site. 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. Of note, it was found that CBUD‑1001 attenuates the cell motility of CRC cells by downregulating the EMT signaling pathway. Thus, CBUD‑1001 may prove to be a promising novel drug candidate for CRC therapy.
View Figures
View References

Related Articles

Journal Cover

October-2020
Volume 57 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Kim S, La MT, Shin M, Kim SW and Kim HK: A novel HDAC1 inhibitor, CBUD‑1001, exerts anticancer effects by modulating the apoptosis and EMT of colorectal cancer cells. Int J Oncol 57: 1027-1038, 2020
APA
Kim, S., La, M.T., Shin, M., Kim, S., & Kim, H. (2020). A novel HDAC1 inhibitor, CBUD‑1001, exerts anticancer effects by modulating the apoptosis and EMT of colorectal cancer cells. International Journal of Oncology, 57, 1027-1038. https://doi.org/10.3892/ijo.2020.5109
MLA
Kim, S., La, M. T., Shin, M., Kim, S., Kim, H."A novel HDAC1 inhibitor, CBUD‑1001, exerts anticancer effects by modulating the apoptosis and EMT of colorectal cancer cells". International Journal of Oncology 57.4 (2020): 1027-1038.
Chicago
Kim, S., La, M. T., Shin, M., Kim, S., Kim, H."A novel HDAC1 inhibitor, CBUD‑1001, exerts anticancer effects by modulating the apoptosis and EMT of colorectal cancer cells". International Journal of Oncology 57, no. 4 (2020): 1027-1038. https://doi.org/10.3892/ijo.2020.5109