2-methoxycinnamaldehyde and Adenocarcinoma-of-Lung

Cinnamomum verum is used to make the spice cinnamon and has been used as a traditional Chinese herbal medicine. We evaluated the anticancer effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the bark of the plant, and its underlying molecular biomarkers associated with carcinogenesis in human lung adenocarcinoma A549 cells. The results show that 2-MCA suppressed proliferation and induced apoptosis as indicated by an upregulation of pro-apoptotic Bax and Bak genes and downregulation of anti-apoptotic Bcl-2 and Bcl-XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase-3 and -9, and morphological characteristics of apoptosis, including plasma membrane blebbing and long comet tail. In addition, 2-MCA also induced lysosomal vacuolation with increased volume of acidic compartment (VAC) and suppressions of nuclear transcription factors nuclear factor-κB (NF-κB) and both topoisomerase I and II activities. Further study reveals that the growth-inhibitory effect of 2-MCA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of 2-MCA against A549 cells is accompanied by downregulations of NF-κB binding activity and proliferative control involving apoptosis and both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and VAC. Our data suggest that 2-MCA could be a potential agent for anticancer therapy.

Topics: Acrolein; Adenocarcinoma; Adenocarcinoma of Lung; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Apoptosis Regulatory Proteins; Cell Line, Tumor; Cinnamomum zeylanicum; Cytochromes c; DNA Topoisomerases, Type I; DNA Topoisomerases, Type II; Humans; Lung Neoplasms; Male; Membrane Potential, Mitochondrial; Mice; Mice, Nude; NF-kappa B; Topoisomerase Inhibitors; Xenograft Model Antitumor Assays