title: Inhibition of NF-κB and metastasis in irinotecan (CPT-11)-resistant LoVo colon cancer cells by thymoquinone via JNK and p38.
abstract: Clinically used chemotherapeutics can effectively eliminate most tumor cells. However, they cause unwanted side effects and result in chemoresistance. To overcome such problems, phytochemicals are now used to treat cancers by means of targeted therapy. Thymoquinone (TQ) is used to treat different cancers (including colon cancer) and is an NF-κB inhibitor. Irinotecan resistant (CPT-11-R) LoVo colon cancer cell line was previous constructed by step-wise CPT-11 challenges to un-treated parental LoVo cells and expresses EGFR/IKKα/β/NF-κB pathway. TQ resulted in reduced total and phosphorylation of IKKα/β and NF-κB and decreased metastasis in CPT-11-R cells. TQ not only reduced activity of ERK1/2 and PI3K but also activated JNK and p38. Furthermore, TQ was also found to suppress metastasis through activation of JNK and p38. Therefore, TQ suppressed metastasis through NF-κB inhibition and activation of JNK and p38 in CPT-11-R LoVo colon cancer cells. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 669-678, 2017.
authors.affiliation: Division of Colorectal Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Chen
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Nien-Hung
authors.initials: NH
authors.lastname: Lee
authors.affiliation: Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei, Taiwan.|Nursing and Management College, Mackay Medicine, Taipei, Taiwan.
authors.forename: Hsi-Hsien
authors.initials: HH
authors.lastname: Hsu
authors.affiliation: Chinese Medicine Department, China Medical University Beigang Hospital, Yunlin, Taiwan.
authors.forename: Tsung-Jung
authors.initials: TJ
authors.lastname: Ho
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Armed Force Taichung General Hospital, Taichung, Taiwan.
authors.forename: Chuan-Chou
authors.initials: CC
authors.lastname: Tu
authors.affiliation: Department of Surgery, School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ray-Jade
authors.initials: RJ
authors.lastname: Chen
authors.affiliation: Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.|Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan.
authors.forename: Yueh-Min
authors.initials: YM
authors.lastname: Lin
authors.affiliation: Department of Biotechnology, Bharathiar University, Coimbatore, India.
authors.forename: Vijaya Padma
authors.initials: VP
authors.lastname: Viswanadha
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.|Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D000077146:Irinotecan; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016227:Benzoquinones; C498143:RELA protein, human; D051996:Transcription Factor RelA; D000077146:Irinotecan; D019869:Phosphatidylinositol 3-Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C003466:thymoquinone; D002166:Camptothecin
keywords: CPT-11-R LoVo colon cancer cells; JNK; NF-κB; Thymoquinone; p38