Novel 1,3,5-triazine derivatives exert potent anti-cervical cancer effects by modulating Bax, Bcl2 and Caspases expression

Chem Biol Drug Des. 2018 Mar;91(3):728-734. doi: 10.1111/cbdd.13133. Epub 2017 Nov 15.

Abstract

This study aimed to develop novel 1,3,5-triazine derivatives as potent anti-cervical cancer agents. The compounds were synthesized in short steps with an excellent yield and characterized via various spectroscopic and analytical methods. A structure-activity relationship study suggested that electron-withdrawing substituents showed greater anticancer activity than electron-donating groups. Compound 7p (p-fluoro) showed the highest activity against cervical cancer cells. In a nude mouse xenograft model inoculated with HeLa cells, 7p showed dose-dependent inhibition of cervical tumour growth. Histopathological examination of excised tumour-bearing tissues showed that 7p improved the microstructure in a dose-dependent manner. Compound 7p also increased the proportions of HeLa cells in G0/G1 and S-phase and significantly decreased that of G2/M-phase. The effects of 7p on C-caspase-3, C-caspase-9, Bcl-2 and Bax expression in HeLa cells were also determined.

Keywords: 1,3,5-triazine; C-caspase-3; HeLa cells; anti-cervical cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Caspase 3 / biosynthesis*
  • Caspase 9 / biosynthesis*
  • Cell Cycle / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects*
  • HeLa Cells
  • Humans
  • Jurkat Cells
  • Mice
  • Mice, Nude
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Triazines* / chemical synthesis
  • Triazines* / chemistry
  • Triazines* / pharmacology
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / biosynthesis*

Substances

  • Antineoplastic Agents
  • BAX protein, human
  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Triazines
  • bcl-2-Associated X Protein
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9