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

  • Kuen-daw Tsai China Medical University Beigang Hospital,Yunlin
  • Jonathan Cherng Medical University of Lublin
  • Yi-Heng Liu China Medical University Beigang Hospital,Yunlin
  • Ta-Wei Chen China Medical University Beigang Hospital,Yunlin
  • Ho-Yiu Wong China Medical University Beigang Hospital,Yunlin
  • Shu-mei Yang China Medical University Beigang Hospital,Yunlin
  • Kuo-Shen Chou Saint Mary's Hospital Luodong, Yilan
  • Jaw-Ming Cherng Saint Mary's Hospital Luodong, Yilan
Keywords: 2-methoxycinnamaldehyde, Antiproliferative, Topoisomerase I, Topoisomerase II, Lysosomal vacuolation, Cytotoxicity, Xenograft

Abstract

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 (ΔΨm) 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.

Keywords: 2-methoxycinnamaldehyde; antiproliferative; topoisomerase I; topoisomerase II; lysosomal vacuolation; cytotoxicity; xenograft

(Published: 7 June 2016)

Citation: Food & Nutrition Research 2016, 60: 31607 - http://dx.doi.org/10.3402/fnr.v60.31607

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Author Biographies

Kuen-daw Tsai, China Medical University Beigang Hospital,Yunlin
Department of Internal Medicine
Jonathan Cherng, Medical University of Lublin
Faculty of Medicine
Yi-Heng Liu, China Medical University Beigang Hospital,Yunlin
Department of Internal Medicine
Ta-Wei Chen, China Medical University Beigang Hospital,Yunlin
Department of Internal Medicine
Ho-Yiu Wong, China Medical University Beigang Hospital,Yunlin
Department of Internal Medicine
Shu-mei Yang, China Medical University Beigang Hospital,Yunlin
Department of Internal Medicine
Kuo-Shen Chou, Saint Mary's Hospital Luodong, Yilan
Department of Family Medicine
Jaw-Ming Cherng, Saint Mary's Hospital Luodong, Yilan
Department of Internal Medicine
Published
2016-06-07
How to Cite
1.
Tsai K- daw, Cherng J, Liu Y-H, Chen T-W, Wong H-Y, Yang S- mei, Chou K-S, Cherng J-M. <em>Cinnamomum verum</em&gt; component 2-methoxycinnamaldehyde: a novel antiproliferative drug inducing cell death through targeting both topoisomerase I and II in human colorectal adenocarcinoma COLO 205 cells. fnr [Internet]. 2016Jun.7 [cited 2019Jun.20];600. Available from: https://foodandnutritionresearch.net/index.php/fnr/article/view/1010
Section
Original Articles