title: Discovery of a novel anti-cancer agent targeting both topoisomerase I and II in hepatocellular carcinoma Hep 3B cells in vitro and in vivo: Cinnamomum verum component 2-methoxycinnamaldehyde.
abstract: Cinnamomum verum 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, in hepatocellular carcinoma Hep 3B cells. The results show that 2-MCA suppressed proliferation and induced apoptosis as indicated by an up-regulation of pro-apoptotic bax and bak genes and down-regulation of anti-apoptotic bcl-2 and bcl-XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase 3 and 9, increase in the DNA content in sub G1, and morphological characteristics of apoptosis. 2-MCA also induced lysosomal vacuolation with increased volume of acidic compartments (VAC), suppressions of nuclear transcription factors NF-κB, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and both topoisomerase I and II activities in a dose-dependent manner. Further study reveals 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 Hep 3B cells is accompanied by downregulations of NF-κB binding activity, inflammatory responses involving COX-2 and PGE2, and proliferative control involving apoptosis, 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: a Department of Internal Medicine , E-Da Hospital, I-Shou University , Kaohsiung , Taiwan ;
authors.forename: Daw-Shyong
authors.initials: DS
authors.lastname: Perng
authors.affiliation: b Sierra College , Rocklin , CA , USA ;
authors.forename: Yu-Hsin
authors.initials: YH
authors.lastname: Tsai
authors.affiliation: c Faculty of Medicine , Medical University of Lublin , Lublin , Poland ;
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cherng
authors.affiliation: d Department of Internal Medicine , Saint Mary's Hospital Luodong , Yilan , Taiwan.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Kuo
authors.affiliation: d Department of Internal Medicine , Saint Mary's Hospital Luodong , Yilan , Taiwan.
authors.forename: Chih-Chung
authors.initials: CC
authors.lastname: Shiao
authors.affiliation: d Department of Internal Medicine , Saint Mary's Hospital Luodong , Yilan , Taiwan.
authors.forename: Jaw-Ming
authors.initials: JM
authors.lastname: Cherng
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002935:Cinnamomum zeylanicum / Q000737:chemistry*; D055808:Drug Discovery; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008819:Mice, Nude; D024301:Plant Bark / Q000737:chemistry; D059004:Topoisomerase I Inhibitors / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D059005:Topoisomerase II Inhibitors / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C017910:2-methoxycinnamaldehyde; D000171:Acrolein
keywords: 2-methoxycinnamaldehyde; Anticancer; Hep 3B cells; lysosomal vacuolation; topoisomerase I; topoisomerase II; volume of acidic compartment