Effects of novel all-trans retinoic acid retinamide derivatives on the proliferation and apoptosis of human lung adenocarcinoma cell line A549 cells

Abstract

The aim of the present study was to synthesize a series of retinamide derivatives using all-trans retinoic acid (ATRA) as raw material and observe their effects on the differentiation and apoptosis of human lung adenocarcinoma A549 cells. Four new synthesized ATRA retinamide derivatives were structurally confirmed by spectral analysis, including 1H-NMR, 13C-NMR, and MS. The results showed that the new ATRA retinamide derivatives significantly decreased the carcinoembryonic antigen secretion of A549 cells, significantly decreased the proliferation of A549 cells in a doseand time-dependent manner, and promoted the apoptosis of A549 cells compared with ATRA. The Western blot assay indicated that the expression of Bcl-2 was decreased more in A549 cells treated with N-(3-trifluoromethylphenyl) retinamide than that in A549 cells treated with ATRA. The results also showed that the effects of N-(3-trifluoromethylphenyl) retinamide on differentiation and apoptosis were the strongest among the newly synthesized ATRA retinamide derivatives. Our results suggested that the effects of novel ATRA retinamide derivatives on increasing the differentiation, decreasing the proliferation, and promoting the apoptosis of A549 cells were greater than those of ATRA. The apoptosis of A549 cells induced by N-(3-trifluoromethylphenyl) retinamide may be related to downregulating the expression of Bcl-2. © 2011 The Pharmaceutical Society of Japan.