Expression of estrogen receptor alpha 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 (ERalpha) 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 ERalpha-negative MDA-MB-231 breast cancer cells, which become ERalpha positive after treatment with a decoy molecule against a regulatory region of the human ERalpha gene. All the plant extracts inhibited cell proliferation and showed no effect on ERalpha 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 ERa gene expression in MDA-MB-231 ERalpha-negative breast cancer cells, and also inhibited cell proliferation.
Lambertini
Elizabeth
E
ER-GenTech, Department of Biochemistry and Molecular Biology, Ferrara University, Ferrara, Italy.
Lampronti
Ilaria
I
Penolazzi
Letizia
L
Khan
Mahmud Tareq Hassan
MT
Ather
Arjumand
A
Giorgi
Gianluca
G
Gambari
Roberto
R
Piva
Roberta
R
D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002849:Chromatography, Gas; D047628:Estrogen Receptor alpha / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D013058:Mass Spectrometry; D008956:Models, Chemical; D053978:Pentacyclic Triterpenes; D010641:Phenotype; D010936:Plant Extracts / Q000378:metabolism* / Q000627:therapeutic use; D010946:Plants, Medicinal; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology; D000094042:Lupanes
D047628:Estrogen Receptor alpha; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D012333:RNA, Messenger; D014157:Transcription Factors; D014315:Triterpenes; C010480:lupeol; D000094042:Lupanes