title: Cinnamomum verum Component 2-Methoxycinnamaldehyde: A Novel Anticancer Agent with Both Anti-Topoisomerase I and II Activities in Human Lung Adenocarcinoma A549 Cells In Vitro and In Vivo.
abstract: 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.
authors.affiliation: Department of Internal Medicine, China Medical University Beigang Hospital, Yunlin, 65152, Taiwan.
authors.forename: Ho-Yiu
authors.initials: HY
authors.lastname: Wong
authors.affiliation: Department of Internal Medicine, China Medical University Beigang Hospital, Yunlin, 65152, Taiwan.|School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan.|Institute of Molecular Biology, National Chung Cheng University, Chiayi, 62102, Taiwan.
authors.forename: Kuen-daw
authors.initials: KD
authors.lastname: Tsai
authors.affiliation: Department of Internal Medicine, China Medical University Beigang Hospital, Yunlin, 65152, Taiwan.
authors.forename: Yi-Heng
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, China Medical University Beigang Hospital, Yunlin, 65152, Taiwan.|School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan.
authors.forename: Shu-mei
authors.initials: SM
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, China Medical University Beigang Hospital, Yunlin, 65152, Taiwan.
authors.forename: Ta-Wei
authors.initials: TW
authors.lastname: Chen
authors.affiliation: Faculty of Medicine, Medical University of Lublin, Lublin, Poland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cherng
authors.affiliation: Department of Family Medicine, Saint Mary's Hospital Luodong, Yilan, 26546, Taiwan.
authors.forename: Kuo-Shen
authors.initials: KS
authors.lastname: Chou
authors.affiliation: Department of Internal Medicine, Saint Mary's Hospital Luodong, Yilan, 26546, Taiwan.
authors.forename: Chen-Mei
authors.initials: CM
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, Saint Mary's Hospital Luodong, Yilan, 26546, Taiwan.
authors.forename: Belen T
authors.initials: BT
authors.lastname: Yao
authors.affiliation: Department of Internal Medicine, Saint Mary's Hospital Luodong, Yilan, 26546, Taiwan.
authors.forename: Jaw-Ming
authors.initials: JM
authors.lastname: Cherng
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000230:Adenocarcinoma / Q000188:drug therapy; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D002935:Cinnamomum zeylanicum / Q000737:chemistry*; D045304:Cytochromes c / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D059003:Topoisomerase Inhibitors / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D059003:Topoisomerase Inhibitors; C017910:2-methoxycinnamaldehyde; D000171:Acrolein; D045304:Cytochromes c; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D004250:DNA Topoisomerases, Type II
keywords: 2-methoxycinnamaldehyde; A549 cells; anticancer; topoisomerase I; topoisomerase II