Anticancer and Immunomodulatory Activities of a Novel Water-Soluble Derivative of Ellipticine

Molecules. 2020 May 1;25(9):2130. doi: 10.3390/molecules25092130.

Abstract

Cancer still remains a major public health concern around the world and the search for new potential antitumor molecules is essential for fighting the disease. This study evaluated the anticancer and immunomodulatory potential of the newly synthetized ellipticine derivate: sodium bromo-5,11-dimethyl-6H-pyrido[4,3-b]carbazole-7-sulfonate (Br-Ell-SO3Na). It was prepared by the chlorosulfonation of 9-bromoellipticine. The ellipticine-7-sulfonic acid itself is not soluble, but its saponification with sodium hydroxide afforded a water-soluble sodium salt. The cytotoxicity of Br-Ell-SO3Na was tested against cancerous (K562 cell line) and non-cancerous cells (Vero cell line and human peripheral blood mononuclear cells (PBMC)) using a Methylthiazoletetrazolium (MTT) assay. Cell cycle arrest was assessed by flow cytometry and the immunomodulatory activity was analyzed through an enzyme-linked immunosorbent assay (ELISA). The results showed that the Br-Ell-SO3Na molecule has specific anticancer activity (IC50 = 35 µM) against the K562 cell line, once no cytotoxicity effect was verified against non-cancerous cells. Cell cycle analysis demonstrated that K562 cells treated with Br-Ell-SO3Na were arrested in the phase S. Moreover, the production of IL-6 increased and the expression of IL-8 was inhibited in the human PBMC treated with Br-Ell-SO3Na. The results demonstrated that Br-Ell-SO3Na is a promising anticancer molecule attested by its noteworthy activity against the K562 tumor cell line and immunomodulatory activity in human PBMC cells.

Keywords: 9-bromoellipticine; antitumor molecule; ellipticine; immunomodulation; sodium 9-bromo-5,11-dimethyl-6H-pyrido[4,3-b]carbazole-7-sulfonate.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Chemistry Techniques, Synthetic
  • Dose-Response Relationship, Drug
  • Ellipticines / chemical synthesis
  • Ellipticines / chemistry*
  • Ellipticines / pharmacology*
  • Humans
  • Immunologic Factors / chemical synthesis
  • Immunologic Factors / chemistry*
  • Immunologic Factors / pharmacology*
  • Immunomodulation / drug effects
  • Molecular Structure
  • Solubility
  • Water

Substances

  • Antineoplastic Agents
  • Ellipticines
  • Immunologic Factors
  • Water