Synergistic antitumor activity of DHA and JQ1 in colorectal carcinoma

Eur J Pharmacol. 2020 Oct 15:885:173500. doi: 10.1016/j.ejphar.2020.173500. Epub 2020 Aug 27.

Abstract

Colon cancer is still a major disease plaguing humans. In this study, we evaluated the synergistic antitumor effects of the combination of BRD4 inhibitor JQ1 and docosahexaenoic acid (DHA) in colon cancer. We demonstrated that simultaneous exposure to JQ1 and DHA resulted in strong synergistic antiproliferative and proapoptotic effects related to inhibition of expression of c-Myc and activation of NF-κB in colon cancer cell lines. At the same time, the synergetic anticancer effect had been confirmed in vivo. For in vivo experiments, JQ1 and DHA resulted in more significant tumor growth inhibition (53.7%) in a human colon cancer HCT116 xenograft model, comparing with the moderate inhibition in JQ1-treated (31.9%) or DHA-treated groups (20.3%). Because DHA is the predominant component of fish oil, our data suggest that this nontoxic dietary supplement could be administered with BRD4 inhibitor during therapy for CRC, which lay an important foundation for the development of therapeutic regimens for CRC.

Keywords: Colon cancer; Docosahexaenoic acid (DHA); Drug combination; JQ1.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Azepines / therapeutic use*
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Docosahexaenoic Acids / therapeutic use*
  • Drug Synergism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mice
  • NF-kappa B / drug effects
  • Proto-Oncogene Proteins c-myc / antagonists & inhibitors
  • Transcription Factors / antagonists & inhibitors
  • Triazoles / therapeutic use*
  • Xenograft Model Antitumor Assays

Substances

  • (+)-JQ1 compound
  • Antineoplastic Agents
  • Azepines
  • BRD4 protein, human
  • Cell Cycle Proteins
  • NF-kappa B
  • Proto-Oncogene Proteins c-myc
  • Transcription Factors
  • Triazoles
  • Docosahexaenoic Acids