title: Ursolic acid exerts anti-cancer activity by suppressing vaccinia-related kinase 1-mediated damage repair in lung cancer cells.
abstract: Many mitotic kinases have been targeted for the development of anti-cancer drugs, and inhibitors of these kinases have been expected to perform well for cancer therapy. Efforts focused on selecting good targets and finding specific drugs to target are especially needed, largely due to the increased frequency of anti-cancer drugs used in the treatment of lung cancer. Vaccinia-related kinase 1 (VRK1) is a master regulator in lung adenocarcinoma and is considered a key molecule in the adaptive pathway, which mainly controls cell survival. We found that ursolic acid (UA) inhibits the catalytic activity of VRK1 via direct binding to the catalytic domain of VRK1. UA weakens surveillance mechanisms by blocking 53BP1 foci formation induced by VRK1 in lung cancer cells, and possesses synergistic anti-cancer effects with DNA damaging drugs. Taken together, UA can be a good anti-cancer agent for targeted therapy or combination therapy with DNA damaging drugs for lung cancer patients.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Seong-Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Hye Guk
authors.initials: HG
authors.lastname: Ryu
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Juhyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore 637551.
authors.forename: Joon
authors.initials: J
authors.lastname: Shin
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore 637551.
authors.forename: Amaravadhi
authors.initials: A
authors.lastname: Harikishore
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Hoe-Yune
authors.initials: HY
authors.lastname: Jung
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Hoe-Youn
authors.initials: HY
authors.lastname: Jung
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Ye Seul
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Ha-Na
authors.initials: HN
authors.lastname: Lyu
authors.affiliation: The Graduate School of Biotechnology and Plant Metabolism Research Center, Kyung-Hee University, Suwon 449-701, Republic of Korea.
authors.forename: Eunji
authors.initials: E
authors.lastname: Oh
authors.affiliation: The Graduate School of Biotechnology and Plant Metabolism Research Center, Kyung-Hee University, Suwon 449-701, Republic of Korea.
authors.forename: Nam-In
authors.initials: NI
authors.lastname: Baek
authors.affiliation: Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Kwan-Yong
authors.initials: KY
authors.lastname: Choi
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore 637551.|Department of Genetic Engineering, College of Life Sciences, Kyung-Hee University, Suwon 449-701, Republic of Korea.
authors.forename: Ho Sup
authors.initials: HS
authors.lastname: Yoon
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.|Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008958:Models, Molecular; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D000097245:Ursolic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004317:Doxorubicin; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D014315:Triterpenes; D000097245:Ursolic Acid; C109890:VRK1 protein, human