(2E)-N,N-dibutyl-3-(4-hydroxy-3-methoxyphenyl)acrylamide induces apoptosis and cell cycle arrest in HL-60 cells.

Background: Ferulic acid is one of the most ubiquitous phenolic compounds in nature, which has antioxidant and anticancer activities. However, ferulic acid derivatives, such as ferulamide have never been reported. Materials and Methods: (2E)-N,N-dibutyl-3-(4-hydroxy-3- methoxyphenyl)acrylamide (compound 8), a ferulamide derivative was synthesized in our laboratory. In this study, HL-60 cells were treated with various concentrations of compound 8, and its effects on cell growth, cell cycle, apoptosis and related measurements were investigated. Results: Compound 8 inhibited cell growth in a concentration- and time-dependent manner with significant cytotoxicity, and the concentration required to inhibit growth by 50% (IC50) was 8.2 IM for 24 h. The cell cycle analysis indicated that compound 8 treated cells were arrested in the G2/M-phase and followed by apoptosis. Microscopic examination showed that treatment with compound 8 displayed typical morphological features of apoptotic cells, with cell shrinking and formation of apoptotic bodies. Reverse transcription-polymerase chain reaction (RT- PCR) analysis showed a dramatic induction of CDK inhibitor p21, which inhibited the expression of cyclin B1, thereby resulting in G2/M phase arrest. After G2/M-phase arrest, cells underwent apoptosis via significant down-regulation of Bcl-2 expression. Conclusion: These results enhance our understanding of the mechanisms of action of compound 8-mediated anticancer effects. Leukemia is classified as myeloid or lymphoid, depending on the cell line which is affected, and is also divided into broad categories of acute or chronic phenotypes. Approximately 33,440 new cases of leukemia are currently