(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.


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 microM 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.


CONCLUSIONS
These results enhance our understanding of the mechanisms of action of compound 8-mediated anticancer effects.
Chen
Chun-Jen
CJ
Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, ROC.
Hsu
Mei-Hua
MH
Kuo
Sheng-Chu
SC
Lai
Ya-Yun
YY
Chung
Jing-Gung
JG
Huang
Li-Jiau
LJ
D000178:Acrylamides / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
C518368:(2E)-N,N-dibutyl-3-(4-hydroxy-3-methoxyphenyl)acrylamide; D000178:Acrylamides; D000970:Antineoplastic Agents; C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein