Inhibitory effect of traditional oriental medicine-derived monoamine oxidase B inhibitor on radioresistance of non-small cell lung cancer

Scientific Reports
Beomseok SonBuHyun Youn

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.

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Citations

Nov 26, 2016·Experimental & Molecular Medicine·Wanyeon KimBuHyun Youn
Sep 22, 2019·Cells·Wanyeon KimBuHyun Youn
Aug 12, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Beomseok SonBuHyun Youn
Sep 10, 2019·International Journal of Radiation Biology·Beomseok SonBuHyun Youn
Jul 5, 2018·Cancer Metastasis Reviews·Wanyeon KimBuHyun Youn
Jul 3, 2019·International Journal of Molecular Sciences·Yasuhisa AnoHiroyuki Nakayama
Aug 3, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Chunyu LiGuohui Li

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Methods Mentioned

BETA
isothermal titration calorimetry
nuclear translocation
immunoprecipitation
enzyme-linked immunosorbent assay
ChIP
xenograft

Software Mentioned

Prism
GraphPad

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