Expression of estrogen receptor α gene in breast cancer cells treated with transcription factor decoy is modulated by Bangladeshi natural plant extracts

The aim of the present study was to determine whether the expression of the estrogen receptor alpha (ER alpha) gene may be a possible target for compounds present in plant extracts from Aegle marmelos and Emblica officinalis, used in traditional Asian medicine in the treatment of tissue inflammation and cancer. To this aim, we evaluated the potential of the selected plant extracts to affect proliferation and differentiation of ER alpha-negative MDA-MB-231 breast cancer cells, which become ER alpha positive after treatment with a decoy molecule against a regulatory region of the human ER alpha gene. All the plant extracts inhibited cell proliferation and showed no effect on ER alpha gene expression, but when they were added in combination with the decoy molecule, a modulatory effect was observed, depending on the extract employed. The extracts exhibiting the greatest effects were those obtained from Aegle marmelos. Gas-chromatography/mass-spectrometry (GC/ MS) analysis enabled us to identify lupeol, a known triterpenoid, as the major bioactive component of A. marmelos plant extracts. Similar to the Aegle marmelos extracts, lupeol was found to stimulate the decoy effect of RA4 DNA sequence, increasing at a high level ER alpha gene expression in MDA-MB-231 ER alpha-negative breast cancer cells, and also inhibited cell proliferation.