title: Inhibitory effect of traditional oriental medicine-derived monoamine oxidase B inhibitor on radioresistance of non-small cell lung cancer.
abstract: Increased survival of cancer cells mediated by high levels of ionizing radiation (IR) reduces the effectiveness of radiation therapy for non-small cell lung cancer (NSCLC). In the present study, danshensu which is a selected component of traditional oriental medicine (TOM) compound was found to reduce the radioresistance of NSCLC by inhibiting the nuclear factor-κB (NF-κB) pathway. Of the various TOM compounds reported to inhibit the IR activation of NF-κB, danshensu was chosen as a final candidate based on the results of structural comparisons with human metabolites and monoamine oxidase B (MAOB) was identified as the putative target enzyme. Danshensu decreased the activation of NF-κB by inhibiting MAOB activity in A549 and NCI-H1299 NSCLC cells. Moreover, it suppressed IR-induced epithelial-to-mesenchymal transition, expressions of NF-κB-regulated prosurvival and proinflammatory genes, and in vivo radioresistance of mouse xenograft models. Taken together, this study shows that danshensu significantly reduces MAOB activity and attenuates NF-κB signaling to elicit the radiosensitization of NSCLC.
authors.affiliation: Department of Integrated Biological Science, Pusan National University, Busan, Republic of Korea.
authors.forename: Beomseok
authors.initials: B
authors.lastname: Son
authors.affiliation: Department of Chemistry, Washington State University, Pullman, Washington, USA.
authors.forename: Se Young
authors.initials: SY
authors.lastname: Jun
authors.affiliation: Department of Integrated Biological Science, Pusan National University, Busan, Republic of Korea.
authors.forename: HyunJeong
authors.initials: H
authors.lastname: Seo
authors.affiliation: Nuclear Science Research Institute, Pusan National University, Busan, Republic of Korea.
authors.forename: HyeSook
authors.initials: H
authors.lastname: Youn
authors.affiliation: Department of Biological Sciences, Pusan National University, Busan, Republic of Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: Nuclear Science Research Institute, Pusan National University, Busan, Republic of Korea.|Department of Biological Sciences, Pusan National University, Busan, Republic of Korea.
authors.forename: Wanyeon
authors.initials: W
authors.lastname: Kim
authors.affiliation: Department of Nanomaterial Engineering and Nanoconvergence Technology, Pusan National University, Miryang, Republic of Korea.
authors.forename: Hyung Kook
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Chemistry, Washington State University, Pullman, Washington, USA.
authors.forename: ChulHee
authors.initials: C
authors.lastname: Kang
authors.affiliation: Department of Integrated Biological Science, Pusan National University, Busan, Republic of Korea.|Department of Chemistry, Washington State University, Pullman, Washington, USA.|Nuclear Science Research Institute, Pusan National University, Busan, Republic of Korea.|Department of Biological Sciences, Pusan National University, Busan, Republic of Korea.
authors.forename: BuHyun
authors.initials: B
authors.lastname: Youn
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D004365:Drugs, Chinese Herbal; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007773:Lactates / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008518:Medicine, East Asian Traditional; D051379:Mice; D008819:Mice, Nude; D008995:Monoamine Oxidase / Q000235:genetics* / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D007773:Lactates; D008996:Monoamine Oxidase Inhibitors; D016328:NF-kappa B; C035055:3,4-dihydroxyphenyllactic acid; D008995:Monoamine Oxidase