title: Allergen-Removed Rhus verniciflua Extract Induces Ovarian Cancer Cell Death via JNK Activation.
abstract: Nuclear factor-[Formula: see text]B (NF-[Formula: see text]B)/Rel transcription factors are best known for their central roles in promoting cell survival in cancer. NF-[Formula: see text]B antagonizes tumor necrosis factor (TNF)-[Formula: see text]-induced apoptosis through a process involving attenuation of the c-Jun-N-terminal kinase (JNK). However, the role of JNK activation in apoptosis induced by negative regulation of NF-[Formula: see text]B is not completely understood. We found that allergen-removed Rhus verniciflua Stokes (aRVS) extract-mediated NF-[Formula: see text]B inhibition induces apoptosis in SKOV-3 ovarian cancer cells via the serial activation of caspases and SKOV-3 cells are most specifically suppressed by aRVS. Here, we show that in addition to activating caspases, aRVS extract negatively modulates the TNF-[Formula: see text]-mediated I[Formula: see text]B/NF-[Formula: see text]B pathway to promote JNK activation, which results in apoptosis. When the cytokine TNF-[Formula: see text] binds to the TNF receptor, I[Formula: see text]B dissociates from NF-[Formula: see text]B. As a result, the active NF-[Formula: see text]B translocates to the nucleus. aRVS extract (0.5[Formula: see text]mg/ml) clearly prevented NF-[Formula: see text]B from mobilizing to the nucleus, resulting in the upregulation of JNK phosphorylation. This subsequently increased Bax activation, leading to marked aRVS-induced apoptosis, whereas the JNK inhibitor SP600125 in aRVS extract treated SKOV-3 cells strongly inhibited Bax. Bax subfamily proteins induced apoptosis through caspase-3. Thus, these results indicate that aRVS extract contains components that inhibit NF-[Formula: see text]B signaling to upregulate JNK activation in ovarian cancer cells and support the potential of aRVS as a therapeutic agent for ovarian cancer.
authors.affiliation: * Division of Bioconvergence, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea.
authors.forename: Se-Hui
authors.initials: SH
authors.lastname: Kang
authors.affiliation: † Department of Physiology, Korea University College of Medicine, Seoul 02841, Republic of Korea.
authors.forename: In-Hu
authors.initials: IH
authors.lastname: Hwang
authors.affiliation: ‡ Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, Korea.
authors.forename: Eunju
authors.initials: E
authors.lastname: Son
authors.affiliation: § East-West Cancer Center, Daejeon University, Daejeon 302-120, Republic of Korea.
authors.forename: Chong-Kwan
authors.initials: CK
authors.lastname: Cho
authors.affiliation: * Division of Bioconvergence, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea.|‡ Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 305-764, Korea.
authors.forename: Jong-Soon
authors.initials: JS
authors.lastname: Choi
authors.affiliation: ¶ Department of Sasang Constitutional Medicine, College of Korean Medicine, Woosuk University, Wanju, Jeonbuk, 55338, Republic of Korea.
authors.forename: Soo-Jung
authors.initials: SJ
authors.lastname: Park
authors.affiliation: ∥ Department of Molecular Medicine, College of Medicine, Keimyung University, Daegu 704-701, Republic of Korea.
authors.forename: Byeong-Churl
authors.initials: BC
authors.lastname: Jang
authors.affiliation: * Division of Bioconvergence, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea.
authors.forename: Kyung-Bok
authors.initials: KB
authors.lastname: Lee
authors.affiliation: * Division of Bioconvergence, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea.
authors.forename: Zee-Won
authors.initials: ZW
authors.lastname: Lee
authors.affiliation: ** Department of Integrative Cancer Center, Woosuk Korean Medicine Hospital, Woosuk University, Jeonju 560-833, Republic of Korea.
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: § East-West Cancer Center, Daejeon University, Daejeon 302-120, Republic of Korea.
authors.forename: Hwa-Seung
authors.initials: HS
authors.lastname: Yoo
authors.affiliation: * Division of Bioconvergence, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea.
authors.forename: Ik-Soon
authors.initials: IS
authors.lastname: Jang
mesh_terms: D000485:Allergens / Q000302:isolation & purification*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D020169:Caspases / Q000378:metabolism; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D029045:Rhus / Q000737:chemistry*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors
chemical_list: D000485:Allergens; D020672:I-kappa B Proteins; D016328:NF-kappa B; D010936:Plant Extracts; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases
keywords: Allergen-Removed Rhus verniciflua Extract; Apoptosis; JNK; NF-B; SKOV-3