title: Molecular Mechanism of Cinnamomum verum Component Cuminaldehyde Inhibits Cell Growth and Induces Cell Death in Human Lung Squamous Cell Carcinoma NCI-H520 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 effects and the molecular mechanisms of cuminaldehyde (CuA), a constituent of the bark of Cinnamomum verum, on human lung squamous cell carcinoma NCI-H520 cells. Specifically, cell viability was evaluated by colorimetric assay; cytotoxicity by LDH release; apoptosis was determined by Western blotting, and morphological analysis with, acridine orange and neutral red stainings and comet assay; topoisomerase I activity was assessed using assay based upon DNA relaxation and topoisomerase II by DNA relaxation plus decatentation of kinetoplast DNA; lysosomal vacuolation and volume of acidic compartments (VAC) were evaluated with neutral red staining. The results show that CuA suppressed proliferation and induced apoptosis as indicated by an up-regulation of pro-apoptotic bax and bak genes and a down-regulation 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 blebbing of the plasma membrane, nuclear condensation, fragmentation, apoptotic body formation, and comet with elevated tail intensity and moment. In addition, CuA also induced lysosomal vacuolation with increased VAC, cytotoxicity, as well as suppressions of both topoisomerase I and II activities in a dose-dependent manner. Further study revealed the growth-inhibitory effect of CuA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of CuA against NCI-H520 cells is accompanied by downregulations of proliferative control involving apoptosis and both topoisomerase I and II activities, and upregulation of lysosomal with increased VAC and cytotoxicity. Similar effects were found in other cell lines, including human lung adenocarcinoma A549 cells and colorectal adenocarcinoma COLO 205 (results not shown). Our data suggest that CuA could be a potential agent for anticancer therapy.
authors.affiliation: 1. Department of Internal Medicine, China Medical University Beigang Hospital, Yunlin, Taiwan ROC; 2. School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan ROC.
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Yang
authors.affiliation: 1. Department of Internal Medicine, China Medical University Beigang Hospital, Yunlin, Taiwan ROC; 2. School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan ROC; 3. Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan ROC.
authors.forename: Kuen-Daw
authors.initials: KD
authors.lastname: Tsai
authors.affiliation: 1. Department of Internal Medicine, China Medical University Beigang Hospital, Yunlin, Taiwan ROC.
authors.forename: Ho-Yiu
authors.initials: HY
authors.lastname: Wong
authors.affiliation: 1. Department of Internal Medicine, China Medical University Beigang Hospital, Yunlin, Taiwan ROC.
authors.forename: Yi-Heng
authors.initials: YH
authors.lastname: Liu
authors.affiliation: 1. Department of Internal Medicine, China Medical University Beigang Hospital, Yunlin, Taiwan ROC.
authors.forename: Ta-Wei
authors.initials: TW
authors.lastname: Chen
authors.affiliation: 4. Faculty of Medicine, Medical University of Lublin, Lublin, Poland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cherng
authors.affiliation: 5. Department of Internal Medicine, Saint Mary's Hospital Luodong, Yilan, Taiwan ROC.
authors.forename: Kwang-Ching
authors.initials: KC
authors.lastname: Hsu
authors.affiliation: 5. Department of Internal Medicine, Saint Mary's Hospital Luodong, Yilan, Taiwan ROC.
authors.forename: Yao-Uh
authors.initials: YU
authors.lastname: Ang
authors.affiliation: 5. Department of Internal Medicine, Saint Mary's Hospital Luodong, Yilan, Taiwan ROC.
authors.forename: Jaw-Ming
authors.initials: JM
authors.lastname: Cherng
keywords: Cuminaldehyde; NCI-H520 cells; anticancer; cytotoxicity; lysosomal vacuolation; topoisomerase I; topoisomerase II; xenograft