A novel all-trans retinoic acid derivative inhibits proliferation and induces apoptosis of myelodysplastic syndromes cell line SKM-1 cells via up-regulating p53.

Abstract Myelodysplastic syndromes (MDS) are a varied set of hematologic neoplasms and a high risk of progression to acute myeloid leukemia (AML). 4-Amino-2-trifluoromethyl-phenyl retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative, play an important role in various types of cancer cells as a tumor inhibitor. However, little is known concerning its antitumor effect on MDS. The cell viability and the percentage of apoptotic cells were used to measure MTT, Flow Cytometry and Hoechst 33342/PI staining. In addition, real-time quantitative RT-PCR (qRT-PCR) and western blotting were used to analyzed the expression of p53, as well as the levels of BNIP3, apoptosis proteins of Caspase-3, BAX and BCL-2. After SKM-1 cells were incubated with DAC, ATRA and ATPR, the viability of the SKM-1 cells was inhibited in a dose- and time-dependent manner. Both Hoechst staining and flow cytometry showed the apoptosis of SKM-1 cells was increased. Moreover, SKM-1 cells treated with ATPR unveiled elevated mRNA and protein levels of p53, BNIP3, BAX and Caspase-3 expression and decreased BCL-2 expression. However, silencing p53 suppressed the pro-apoptosis function of ATPR. Consequently, these data provide the first evidence for ATPR increased apoptosis in SKM-1 cells by p53 that is mutually dependent on and obligatorily linked to BNIP3 gene activation. Highlights • DAC, ATRA and ATPR inhibited the metabolic activity of SKM-1 Cells. • DAC, ATRA and ATPR induced the apoptosis of SKM-1 Cells. • p53 induced SKM-1 cells apoptosis via BNIP3, BAX, BCL-2 and Caspase-3. • ATPR up-regulated the protein level of p53 and induced SKM-1 cell apoptosis via p53. [ABSTRACT FROM AUTHOR]