Aims: To explore the effect and probable mechanism of a synthetic retinoid 4-amino-2-tri-fluoromethylphenylester (ATPR) on apoptosis of MDA-MB-231 breast cancer cells. Materials and
Methods: MTT assayswere performed to measure the proliferation of MDA-MB-231 cells treated with different concentrations of alltransretinoic acid (ATRA) and ATPR. Morphologic changes were observed by microscopy. The apoptosis ratesand cell cycling of MDA-MB-231 cells treated with ATRA or ATPR were assessed using flow cytometry analysis.Expression of retinoic acid receptor and phosphorylation of ERK, JNK, p38 proteins were detected by Westernblotting.
Results: Treatment of the cells with the addition of 15 μmol/L ATPR for 48 h clearly demonstratedreduced cell numbers and deformed cells, whereas no changes in the number and morphology were observedafter treatment with ATRA. The apoptosis rate was 33.2% after breast cancer MDA-MB-231 cells were treatedby ATPR (15 μmol/L) whereas ATRA (15 μmol/L) had no apoptotic effect. ATPR inhibited the phosphorylationof ERK, JNK, and p38 while ATRA had no significant effect. ATPR inhibited the expression of BiP and increasedthe expression of Chop at the protein level compared with control groups, ATRA and ATPR both decreasedthe protein expression of RXR α, ATPR reduced the protein expression of RARβ and RXRβ while ATRA didnot decrease RARβ or RXRβ.
Conclusions: ATPR could induce apoptosis of breast cancer MDA-MB-231 cells,possible mechanisms being binding to RARβ/RXRβ heterodimers, then activation of ER stress involving theMAPK pathway.