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

• Published in: Food & nutrition research Vol. 60; no. 1; p. 31607
• Main Authors: Tsai, Kuen-daw, Cherng, Jonathan, Liu, Yi-Heng, Chen, Ta-Wei, Wong, Ho-Yiu, Yang, Shu-mei, Chou, Kuo-Shen, Cherng, Jaw-Ming
• Format: Journal Article
• Language: English
• Published: Sweden Taylor & Francis 01.01.2016; Swedish Nutrition Foundation, SNF; Co-Action Publishing; Swedish Nutrition Foundation
• Subjects: 2-methoxycinnamaldehyde; Acridine orange; Adenocarcinoma; animal disease models; Annexin V; Anticancer properties; antiproliferative; Apoptosis; Bioassays; Biocompatibility; Biomarkers; Cancer; cancer therapy; carcinogenesis; Caspase; Caspase-3; Cell death; cell growth; Cell viability; Cinnamomum verum; Cinnamon; Colorimetry; Comet assay; cortex; Cytotoxicity; Damage detection; Deoxyribonucleic acid; DNA; DNA topoisomerase; DNA topoisomerase (ATP-hydrolysing); enzyme activity; enzyme inhibition; Flow cytometry; Hepatocellular carcinoma; hepatoma; Herbal medicine; herbal medicines; human diseases; humans; kinetoplast DNA; Liver cancer; Lung cancer; Lungs; lysosomal vacuolation; manufacturing; Membrane potential; Mitochondria; mitochondrial membrane; Molting; Morphology; Original; Physical characteristics; Squamous cell carcinoma; staining; topoisomerase I; topoisomerase II; Toxicity; Tumor cell lines; Tumorigenesis; xenograft; topoisomerase II; lysosomal vacuolation; xenograft; 2-methoxycinnamaldehyde; antiproliferative; cytotoxicity; topoisomerase I
• ISSN: 1654-6628; 1654-661X; 1654-661X
• DOI: 10.3402/fnr.v60.31607

Cinnamomum verum is used to manufacture the spice cinnamon. In addition, the plant has been used as a Chinese herbal medication. 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. The results demonstrate that 2-MCA inhibited proliferation and induced apoptosis as implicated by mitochondrial membrane potential (ΔΨ 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. 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.