Anticancer activities of a benzimidazole compound through sirtuin inhibition in colorectal cancer

Future Med Chem. 2018 Sep 1;10(17):2039-2057. doi: 10.4155/fmc-2018-0052. Epub 2018 Aug 1.

Abstract

Aim: This study aims to investigate the mode of action of a novel sirtuin inhibitor (BZD9L1) and its associated molecular pathways in colorectal cancer (CRC) cells.

Materials & methods: BZD9L1 was tested against metastatic CRC cell lines to evaluate cytotoxicity, cell cycle and apoptosis, senescence, apoptosis related genes and protein expressions, as well as effect against major cancer signaling pathways.

Results & conclusion: BZD9L1 reduced the viability, cell migration and colony forming ability of both HCT 116 and HT-29 metastatic CRC cell lines through apoptosis. BZD9L1 regulated major cancer pathways differently in CRC with different mutation profiles. BZD9L1 exhibited anticancer activities as a cytotoxic drug in CRC and as a promising therapeutic strategy in CRC treatment.

Keywords: BZD9L1; colorectal cancer; sirtuin; targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Benzimidazoles / chemistry*
  • Benzimidazoles / pharmacology*
  • Cell Cycle / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Molecular Targeted Therapy
  • Sirtuins / antagonists & inhibitors*
  • Sirtuins / metabolism

Substances

  • Antineoplastic Agents
  • Benzimidazoles
  • Sirtuins