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

Beomseok Son; Se Young Jun; HyunJeong Seo; HyeSook Youn; Hee Jung Yang; Wanyeon Kim; Hyung Kook Kim; ChulHee Kang; BuHyun Youn

doi:10.1038/srep21986

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

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

Beomseok Son, Se Young Jun, HyunJeong Seo, HyeSook Youn, Hee Jung Yang, Wanyeon Kim, Hyung Kook Kim, ChulHee Kang and BuHyun Youn

Scientific reports, Vol.6(1), pp.21986-21986

02/24/2016

DOI: https://doi.org/10.1038/srep21986

Handle:

https://hdl.handle.net/2376/107824

PMCID: PMC4764943

PMID: 26906215

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Abstract

Epithelial-Mesenchymal Transition - radiation effects

Humans

Lung Neoplasms - metabolism

Gamma Rays - therapeutic use

Gene Expression Regulation, Neoplastic

Epithelial-Mesenchymal Transition - drug effects

Lung Neoplasms - pathology

NF-kappa B - metabolism

Monoamine Oxidase - genetics

Medicine, East Asian Traditional

Carcinoma, Non-Small-Cell Lung - pathology

Lactates - pharmacology

Lung Neoplasms - genetics

Monoamine Oxidase Inhibitors - pharmacology

Drugs, Chinese Herbal

Carcinoma, Non-Small-Cell Lung - genetics

Carcinoma, Non-Small-Cell Lung - metabolism

Lung Neoplasms - therapy

Radiation Tolerance - drug effects

Xenograft Model Antitumor Assays

Carcinoma, Non-Small-Cell Lung - therapy

Animals

NF-kappa B - genetics

Mice, Nude

Cell Line, Tumor

Mice

Antineoplastic Agents, Phytogenic - pharmacology

Monoamine Oxidase - metabolism

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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Title: Inhibitory effect of traditional oriental medicine-derived monoamine oxidase B inhibitor on radioresistance of non-small cell lung cancer
Creators: Beomseok Son - Department of Integrated Biological Science, Pusan National University, Busan, Republic of Korea
Se Young Jun - Department of Chemistry, Washington State University, Pullman, Washington, USA
HyunJeong Seo - Department of Integrated Biological Science, Pusan National University, Busan, Republic of Korea
HyeSook Youn - Nuclear Science Research Institute, Pusan National University, Busan, Republic of Korea
Hee Jung Yang - Department of Biological Sciences, Pusan National University, Busan, Republic of Korea
Wanyeon Kim - Department of Biological Sciences, Pusan National University, Busan, Republic of Korea
Hyung Kook Kim - Department of Nanomaterial Engineering and Nanoconvergence Technology, Pusan National University, Miryang, Republic of Korea
ChulHee Kang - Department of Chemistry, Washington State University, Pullman, Washington, USA
BuHyun Youn - Department of Biological Sciences, Pusan National University, Busan, Republic of Korea
Publication Details: Scientific reports, Vol.6(1), pp.21986-21986
Academic Unit: Chemistry, Department of
Publisher: England
Identifiers: 99900547292401842
Language: English
Resource Type: Journal article