Cinnamomum verum component 2-methoxycinnamaldehyde: a novel antiproliferative drug
inducing cell death through targeting both topoisomerase I and II in human colorectal
adenocarcinoma COLO 205 cells
Sammanfattning
Background: Cinnamomum verum is used to manufacture the spice cinnamon. In addition, the
plant has been used as a Chinese herbal medication.
Methods: We investigated the antiproliferative effect of 2-methoxycinnamaldehyde (2-MCA), a
constituent of the cortex of the plant, and the molecular biomarkers associated with tumorigenesis in
human colorectal adenocarcinoma COLO 205 cells. Specifically, cell viability was evaluated by
colorimetric assay; apoptosis was determined by flow cytometry and morphological analysis with
bright field, acridine orange, and neutral red stainings, as well as comet assay; topoisomerase I
activity was determined by assay based upon DNA relaxation and topoisomerase II by DNA
relaxation plus decatentation of kinetoplast DNA; lysosomal vacuolation and volume of acidic
compartments (VACs) were determined by neutral red staining.
Results: The results demonstrate that 2-MCA inhibited proliferation and induced apoptosis as
implicated by mitochondrial membrane potential (??m) loss, activation of both caspase-3 and -9,
increase of annexin V+PI+ cells, as well as morphological characteristics of apoptosis. Furthermore,
2-MCA also induced lysosomal vacuolation with elevated VAC, cytotoxicity, and inhibitions of
topoisomerase I as well as II activities. Additional study demonstrated the antiproliferative effect of 2
-MCA found in a nude mice model.
Conclusions: Our data implicate that the antiproliferative activity of 2-MCA in vitro involved
downregulation of cell growth markers, both topoisomerase I and II, and upregulation of pro-apoptotic
molecules, associated with increased lysosomal vacuolation. In vivo 2-MCA reduced the tumor
burden that could have significant clinical impact. Indeed, similar effects were found in other tested
cell lines, including human hepatocellular carcinoma SK-Hep-1 and Hep 3B, lung adenocarcinoma
A549 and squamous cell carcinoma NCI-H520, and T-lymphoblastic MOLT-3 (results not shown). Our
data implicate that 2-MCA could be a potential agent for anticancer therapy.