A Novel All-Trans Retinoid Acid Derivative 4-Amino-2-Trifluoromethyl-Phenyl Retinate Modulates Growth Arrest and Apoptosis of Human Breast Cancer Cell MDA-MB-231
4-Amino-2-trifluoromethyl-phenyl retinate (ATPR) is a novel All-trans Retinoid Acid (ATRA) derivative. The primary aim of this study was to characterize whether ATPR could contribute to growth arrest and apoptosis of breast cancer cell MDA-MB-231. MDA-MB-231 cells were exposed to ATPR. MTT assay was performed to detect the proliferation. Flow cytometry analysis was used to reveal the cell cycle distribution. RT-PCR was performed to reflect the transcription level of cell cycle protein p21 and cyclinD1. Hoechst staining was used to examine cell apoptosis. Western blot analysis was performed to detect the expression levels of p-p38, total p38, p53, iASPP, apoptosis-associated proteins Bcl-2, Bax, caspase-3. The cell proliferation was decreased in a concentration- and time-dependent manner by ATPR. The ATPR mediated G0-G1 phase arrest on MDA-MB-231 and promoted apoptosis of MDA-MB-231. In addition, the ATPR could increase the expression of p53 and decrease the expression of iASPP and the phosphorylation of p38. After combined with SB203580, ATPR could induce an enhancement of transcription level of p21, a reduction of transcription level of cyclinD1, an increase in Bax expression, a decrease in Bcl-2 level. Besides, the p53 was elevated while the expression of iASPP was declined more obviously, and that caused a further decrease in the phosphorylation of p38. These results suggested that ATPR contributed to apoptosis and growth inhibition of MDA-MB-231 in a time- and dose-dependently. The mechanism might be related to disruption of p38 signaling and activation of p53.
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