Semisynthetic oleanane triterpenoids inhibit migration and invasion of human breast cancer cells through downregulated expression of the ITGB1/PTK2/PXN pathway

Chem Biol Interact. 2017 Apr 25;268:136-147. doi: 10.1016/j.cbi.2017.03.008. Epub 2017 Mar 18.

Abstract

This paper reports a study on the role of two synthetic derivatives of oleanolic acid (OA), HIMOXOL and Br-HIMOLID, in the regulation of cell migration and invasion and the underlying molecular mechanisms of breast cancer cells. The effect of the compounds on four breast cancer cell lines (MCF7, MDA-MB-231, MDA-MB-468, and T-47D) and also on noncancerous breast cells, MCF-12A, was reported. The compounds had no effect on the migration of MCF-12A cells. However, both the derivatives revealed a higher cytotoxicity than the maternal compound OA, and in sub-cytotoxic concentrations, they decreased the migration of MCF7, MDA-MB-231, and MDA-MB-468 breast cancer cells and also the invasion of MCF7 and MDA-MB-231 cells; although, the derivatives had no effect on the migration and invasion of T-47D cells. Both the derivatives of OA inhibited the cell migratory and invasive abilities of breast cancer cells by downregulating the expressions of ITGB1, PTK2, and PXN genes and by decreasing the phosphorylation status and the level of its respective proteins (integrin β1, FAK, and paxillin, respectively). This study is the first to report the antimigratory and anti-invasive activities of HIMOXOL and Br-HIMOLID in breast cancer cells.

Keywords: Breast cancer; Invasion; Migration; Semisynthetic triterpenoids.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Cell Line, Tumor / drug effects
  • Cell Movement / drug effects
  • Down-Regulation
  • Focal Adhesion Kinase 1 / genetics
  • Focal Adhesion Kinase 1 / metabolism*
  • Humans
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism*
  • Neoplasm Invasiveness
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / pharmacology
  • Paxillin / genetics
  • Paxillin / metabolism
  • Signal Transduction

Substances

  • 12-bromo-3-hydroxyimonoolean-28-13-olide
  • Antineoplastic Agents
  • Integrin beta1
  • PXN protein, human
  • Paxillin
  • methyl 3-hydroxyimino-11-oxoolean-12-en-28-oate
  • Oleanolic Acid
  • Focal Adhesion Kinase 1
  • PTK2 protein, human