title: Brazilin Isolated from Caesalpinia sappan suppresses nuclear envelope reassembly by inhibiting barrier-to-autointegration factor phosphorylation.
abstract: To date, many anticancer drugs have been developed by directly or indirectly targeting microtubules, which are involved in cell division. Although this approach has yielded many anticancer drugs, these drugs produce undesirable side effects. An alternative strategy is needed, and targeting mitotic exit may be one alternative approach. Localization of phosphorylated barrier-to-autointegration factor (BAF) to the chromosomal core region is essential for nuclear envelope compartment relocalization. In this study, we isolated brazilin from Caesalpinia sappan Leguminosae and demonstrated that it inhibited BAF phosphorylation in vitro and in vivo. Moreover, we demonstrated direct binding between brazilin and BAF. The inhibition of BAF phosphorylation induced abnormal nuclear envelope reassembly and cell death, indicating that perturbation of nuclear envelope reassembly could be a novel approach to anticancer therapy. We propose that brazilin isolated from C. sappan may be a new anticancer drug candidate that induces cell death by inhibiting vaccinia-related kinase 1-mediated BAF phosphorylation.
authors.affiliation: Department of Life Sciences (S.-H.K., H.-N.L., Y.S.K., W.K., S.K., K.-T.K.), Division of Integrative Biosciences and Biotechnology (J.-K.L., K.-Y.C., K.-T.K.), Pohang University of Science and Technology, Pohang, South Korea; Graduate School of Biotechnology and Plant Metabolism Research Center, Kyung-Hee University, Suwon, South Korea (N.-I.B.); and Department of Nuclear Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (Y.H.J., H.W.L., J.L.).
authors.forename: Seong-Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Life Sciences (S.-H.K., H.-N.L., Y.S.K., W.K., S.K., K.-T.K.), Division of Integrative Biosciences and Biotechnology (J.-K.L., K.-Y.C., K.-T.K.), Pohang University of Science and Technology, Pohang, South Korea; Graduate School of Biotechnology and Plant Metabolism Research Center, Kyung-Hee University, Suwon, South Korea (N.-I.B.); and Department of Nuclear Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (Y.H.J., H.W.L., J.L.).
authors.forename: Ha-Na
authors.initials: HN
authors.lastname: Lyu
authors.affiliation: Department of Life Sciences (S.-H.K., H.-N.L., Y.S.K., W.K., S.K., K.-T.K.), Division of Integrative Biosciences and Biotechnology (J.-K.L., K.-Y.C., K.-T.K.), Pohang University of Science and Technology, Pohang, South Korea; Graduate School of Biotechnology and Plant Metabolism Research Center, Kyung-Hee University, Suwon, South Korea (N.-I.B.); and Department of Nuclear Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (Y.H.J., H.W.L., J.L.).
authors.forename: Ye Seul
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Life Sciences (S.-H.K., H.-N.L., Y.S.K., W.K., S.K., K.-T.K.), Division of Integrative Biosciences and Biotechnology (J.-K.L., K.-Y.C., K.-T.K.), Pohang University of Science and Technology, Pohang, South Korea; Graduate School of Biotechnology and Plant Metabolism Research Center, Kyung-Hee University, Suwon, South Korea (N.-I.B.); and Department of Nuclear Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (Y.H.J., H.W.L., J.L.).
authors.forename: Yong Hyun
authors.initials: YH
authors.lastname: Jeon
authors.affiliation: Department of Life Sciences (S.-H.K., H.-N.L., Y.S.K., W.K., S.K., K.-T.K.), Division of Integrative Biosciences and Biotechnology (J.-K.L., K.-Y.C., K.-T.K.), Pohang University of Science and Technology, Pohang, South Korea; Graduate School of Biotechnology and Plant Metabolism Research Center, Kyung-Hee University, Suwon, South Korea (N.-I.B.); and Department of Nuclear Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (Y.H.J., H.W.L., J.L.).
authors.forename: Wanil
authors.initials: W
authors.lastname: Kim
authors.affiliation: Department of Life Sciences (S.-H.K., H.-N.L., Y.S.K., W.K., S.K., K.-T.K.), Division of Integrative Biosciences and Biotechnology (J.-K.L., K.-Y.C., K.-T.K.), Pohang University of Science and Technology, Pohang, South Korea; Graduate School of Biotechnology and Plant Metabolism Research Center, Kyung-Hee University, Suwon, South Korea (N.-I.B.); and Department of Nuclear Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (Y.H.J., H.W.L., J.L.).
authors.forename: Sangjune
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Life Sciences (S.-H.K., H.-N.L., Y.S.K., W.K., S.K., K.-T.K.), Division of Integrative Biosciences and Biotechnology (J.-K.L., K.-Y.C., K.-T.K.), Pohang University of Science and Technology, Pohang, South Korea; Graduate School of Biotechnology and Plant Metabolism Research Center, Kyung-Hee University, Suwon, South Korea (N.-I.B.); and Department of Nuclear Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (Y.H.J., H.W.L., J.L.).
authors.forename: Jong-Kwan
authors.initials: JK
authors.lastname: Lim
authors.affiliation: Department of Life Sciences (S.-H.K., H.-N.L., Y.S.K., W.K., S.K., K.-T.K.), Division of Integrative Biosciences and Biotechnology (J.-K.L., K.-Y.C., K.-T.K.), Pohang University of Science and Technology, Pohang, South Korea; Graduate School of Biotechnology and Plant Metabolism Research Center, Kyung-Hee University, Suwon, South Korea (N.-I.B.); and Department of Nuclear Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (Y.H.J., H.W.L., J.L.).
authors.forename: Ho Won
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Life Sciences (S.-H.K., H.-N.L., Y.S.K., W.K., S.K., K.-T.K.), Division of Integrative Biosciences and Biotechnology (J.-K.L., K.-Y.C., K.-T.K.), Pohang University of Science and Technology, Pohang, South Korea; Graduate School of Biotechnology and Plant Metabolism Research Center, Kyung-Hee University, Suwon, South Korea (N.-I.B.); and Department of Nuclear Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (Y.H.J., H.W.L., J.L.).
authors.forename: Nam-In
authors.initials: NI
authors.lastname: Baek
authors.affiliation: Department of Life Sciences (S.-H.K., H.-N.L., Y.S.K., W.K., S.K., K.-T.K.), Division of Integrative Biosciences and Biotechnology (J.-K.L., K.-Y.C., K.-T.K.), Pohang University of Science and Technology, Pohang, South Korea; Graduate School of Biotechnology and Plant Metabolism Research Center, Kyung-Hee University, Suwon, South Korea (N.-I.B.); and Department of Nuclear Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (Y.H.J., H.W.L., J.L.).
authors.forename: Kwan-Yong
authors.initials: KY
authors.lastname: Choi
authors.affiliation: Department of Life Sciences (S.-H.K., H.-N.L., Y.S.K., W.K., S.K., K.-T.K.), Division of Integrative Biosciences and Biotechnology (J.-K.L., K.-Y.C., K.-T.K.), Pohang University of Science and Technology, Pohang, South Korea; Graduate School of Biotechnology and Plant Metabolism Research Center, Kyung-Hee University, Suwon, South Korea (N.-I.B.); and Department of Nuclear Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (Y.H.J., H.W.L., J.L.).
authors.forename: Jaetae
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Life Sciences (S.-H.K., H.-N.L., Y.S.K., W.K., S.K., K.-T.K.), Division of Integrative Biosciences and Biotechnology (J.-K.L., K.-Y.C., K.-T.K.), Pohang University of Science and Technology, Pohang, South Korea; Graduate School of Biotechnology and Plant Metabolism Research Center, Kyung-Hee University, Suwon, South Korea (N.-I.B.); and Department of Nuclear Medicine, Kyungpook National University School of Medicine, Daegu, South Korea (Y.H.J., H.W.L., J.L.) ktk@postech.ac.kr.
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D001578:Benzopyrans / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D029911:Caesalpinia / Q000737:chemistry*; D016923:Cell Death / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D009685:Nuclear Envelope / Q000187:drug effects* / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013692:Telophase / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C501959:BANF1 protein, human; D001578:Benzopyrans; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; C109890:VRK1 protein, human; C044362:brazilin