J Cancer 2016; 7(3):251-261. doi:10.7150/jca.13689

Research Paper

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

Shu-mei Yang1,2, Kuen-daw Tsai1,2,3, Ho-Yiu Wong1, Yi-Heng Liu1, Ta-Wei Chen1, Jonathan Cherng4, Kwang-Ching Hsu5, Yao-Uh Ang5, Jaw-Ming Cherng 5✉

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
4. Faculty of Medicine, Medical University of Lublin, Lublin, Poland
5. Department of Internal Medicine, Saint Mary's Hospital Luodong, Yilan, Taiwan ROC

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.

Keywords: Cuminaldehyde, anticancer, NCI-H520 cells, topoisomerase I, topoisomerase II, lysosomal vacuolation, cytotoxicity, xenograft

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How to cite this article:
Yang Sm, Tsai Kd, Wong HY, Liu YH, Chen TW, Cherng J, Hsu KC, Ang YU, Cherng JM. 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. J Cancer 2016; 7(3):251-261. doi:10.7150/jca.13689. Available from http://www.jcancer.org/v07p0251.htm