title: Cinnamomum verum ingredient 2-methoxycinnamaldehyde: a new antiproliferative drug targeting topoisomerase I and II in human lung squamous cell carcinoma NCI-H520 cells.
abstract: Cinnamomum verum 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 lung squamous cell carcinoma NCI-H520 cells. The effects of 2-MCA on cell growth, cytotoxicity, apoptosis, and topoisomerase I and II activities in human lung squamous cell carcinoma NCI-H520 cells were evaluated in vitro and in vivo. The results showed that 2-MCA inhibited proliferation and induced apoptosis as implicated by mitochondrial membrane potential (ΔΨm) loss, activation of both caspase 3 and caspase 9, as well as morphological characteristics of apoptosis. Furthermore, 2-MCA also induced lysosomal vacuolation with elevated volume of acidic compartment and cytotoxicity, and inhibited topoisomerase I as well as II activities. Additional study showed the antiproliferative effect of 2-MCA in a nude mice model. In short, our data imply that the antiproliferative activity of 2-MCA in vitro involved downregulation of cell growth markers, both topoisomerase I and II, and upregulation of proapoptotic molecules, associated with increased lysosomal vacuolation. In vivo, 2-MCA reduced the tumor size, which could have had a significant clinical impact. Our data imply that 2-MCA may be a potential agent for chemoprevention as well as anticancer therapy.
authors.affiliation: aDepartment of Internal Medicine, China Medical University Beigang Hospital, Yunlin bDepartment of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung cDepartment of Life Science, Institute of Molecular Biology, National Chung Cheng University, Chiayi dDepartment of Internal Medicine, Saint Mary's Hospital Luodong, Yilan, Taiwan, Republic of China eEnglish Division, Department of Medicine, Faculty of Medicine, Medical University of Lublin, Lublin, Poland.
authors.forename: Yi-Heng
authors.initials: YH
authors.lastname: Liu
authors.forename: Kuen-Daw
authors.initials: KD
authors.lastname: Tsai
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Yang
authors.forename: Ho-Yiu
authors.initials: HY
authors.lastname: Wong
authors.forename: Ta-Wei
authors.initials: TW
authors.lastname: Chen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cherng
authors.forename: Jaw-Ming
authors.initials: JM
authors.lastname: Cherng
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D027424:Cinnamomum / Q000737:chemistry*; D004264:DNA Topoisomerases, Type I / Q000737:chemistry*; D004250:DNA Topoisomerases, Type II; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000075223:Poly-ADP-Ribose Binding Proteins / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000075223:Poly-ADP-Ribose Binding Proteins; C017910:2-methoxycinnamaldehyde; D000171:Acrolein; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human