title: Cuminaldehyde from Cinnamomum verum Induces Cell Death through Targeting Topoisomerase 1 and 2 in Human Colorectal Adenocarcinoma COLO 205 Cells.
abstract: Cinnamomum verum, also called true cinnamon tree, is employed to make the seasoning cinnamon. Furthermore, the plant has been used as a traditional Chinese herbal medication. We explored the anticancer effect of cuminaldehyde, an ingredient of the cortex of the plant, as well as the molecular biomarkers associated with carcinogenesis in human colorectal adenocarcinoma COLO 205 cells. The results show that cuminaldehyde suppressed growth and induced apoptosis, as proved by depletion of the mitochondrial membrane potential, activation of both caspase-3 and -9, and morphological features of apoptosis. Moreover, cuminaldehyde also led to lysosomal vacuolation with an upregulated volume of acidic compartment and cytotoxicity, together with inhibitions of both topoisomerase I and II activities. Additional study shows that the anticancer activity of cuminaldehyde was observed in the model of nude mice. Our results suggest that the anticancer activity of cuminaldehyde in vitro involved the suppression of cell proliferative markers, topoisomerase I as well as II, together with increase of pro-apoptotic molecules, associated with upregulated lysosomal vacuolation. On the other hand, in vivo, cuminaldehyde diminished the tumor burden that would have a significant clinical impact. Furthermore, similar effects were observed in other tested cell lines. In short, our data suggest that cuminaldehyde could be a drug for chemopreventive or anticancer therapy.
authors.affiliation: Department of Internal Medicine, China Medical University Beigang Hospital, Yunlin 65152, Taiwan. d4295@yahoo.com.tw.|School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan. d4295@yahoo.com.tw.|Institute of Molecular Biology, National Chung Cheng University, Chiayi 62102, Taiwan. d4295@yahoo.com.tw.
authors.forename: Kuen-Daw
authors.initials: KD
authors.lastname: Tsai
authors.affiliation: Department of Internal Medicine, China Medical University Beigang Hospital, Yunlin 65152, Taiwan. yeeheng6061@gmail.com.
authors.forename: Yi-Heng
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, China Medical University Beigang Hospital, Yunlin 65152, Taiwan. slowfish1234@yahoo.com.tw.
authors.forename: Ta-Wei
authors.initials: TW
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, China Medical University Beigang Hospital, Yunlin 65152, Taiwan. kd2624@yahoo.com.tw.|School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan. kd2624@yahoo.com.tw.
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, China Medical University Beigang Hospital, Yunlin 65152, Taiwan. pk1977wong@gmail.com.
authors.forename: Ho-Yiu
authors.initials: HY
authors.lastname: Wong
authors.affiliation: Faculty of Medicine, Medical University of Lublin, Lublin 20-059, Poland. jcherngca@yahoo.com.tw.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cherng
authors.affiliation: Department of Family Medicine, Saint Mary's Hospital Luodong, Yilan 26546, Taiwan. smh01062@smh.org.tw.
authors.forename: Kuo-Shen
authors.initials: KS
authors.lastname: Chou
authors.affiliation: Department of Internal Medicine, Saint Mary's Hospital Luodong, Yilan 26546, Taiwan. happy.professor@yahoo.com.|St. Mary's Junior College of Medicine, Nursing and Management, Yilan 26644, Taiwan. happy.professor@yahoo.com.
authors.forename: Jaw-Ming
authors.initials: JM
authors.lastname: Cherng
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001547:Benzaldehydes / Q000302:isolation & purification / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002935:Cinnamomum zeylanicum / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000081007:Cymenes; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D015398:Signal Transduction / Q000187:drug effects; D059004:Topoisomerase I Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001547:Benzaldehydes; D000081007:Cymenes; D010936:Plant Extracts; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D004250:DNA Topoisomerases, Type II; C007165:cuminaldehyde
keywords: antiproliferative; cuminaldehyde; lysosomal vacuolation; topoisomerase I; topoisomerase II; xenograft