title: Nimbolide induces apoptosis in human nasopharyngeal cancer cells.
abstract: Nasopharyngeal carcinoma (NPC), a tumor arising from epithelial cells that cover the surface and line the nasopharynx, is a rare malignancy worldwide but is prevalent in certain geographical areas, such as Southern Asia (Taiwan, Hong Kong, Singapore, Malaysia, and Southern China) and North Africa. Despite advances in diagnostic techniques and improvements in treatment modalities, the prognosis of NPC remains poor. Therefore, an effective chemotherapy regimen that enhances tumor sensitivity to chemotherapeutics is urgently required. Nimbolide, derived from Azadirachta indica, has a wide range of beneficial effects, including anti-inflammatory and anticancer properties. The present study evaluated the antitumor activity of nimbolide in NPC cells and its underlying mechanisms. Our results revealed that the treatment of HONE-1 cells with nimbolide potently inhibited cell viability. Moreover, nimbolide led to cell cycle arrest, which subsequently activated caspase-3, -8, and -9 and poly (ADP-ribose) polymerase to induce cell apoptosis. Moreover, nimbolide induced Bik, Bax, and t-Bid expression in HONE-1 cells. The results indicated that nimbolide induces apoptosis through the modulation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathways. Nimbolide induces apoptosis in human NPC cells and is a potential chemopreventive agent against NPC proliferation. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 2085-2092, 2017.
authors.affiliation: Department of Pharmacy, Changhua Christian Hospital, Changhua, 500, Taiwan.|College of Health Sciences, Chang Jung Christian University, Tainan, 71101, Taiwan.|Department of Recreation and Holistic Wellness, Mingdao University, Changhua, 52345, Taiwan.
authors.forename: Su-Yu
authors.initials: SY
authors.lastname: Chien
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua, 500, Taiwan.
authors.forename: Ching-Hui
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Cancer Research Center, Changhua Christian Hospital, Changhua, 500, Taiwan.
authors.forename: Chia-Chieh
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Cancer Research Center, Changhua Christian Hospital, Changhua, 500, Taiwan.
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Chuang
authors.affiliation: Cancer Research Center, Changhua Christian Hospital, Changhua, 500, Taiwan.
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Lo
authors.affiliation: Cancer Research Center, Changhua Christian Hospital, Changhua, 500, Taiwan.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Hsi
authors.affiliation: Cancer Research Center, Changhua Christian Hospital, Changhua, 500, Taiwan.|School of Optometry, Chung Shan Medical University, Taichung, 40201, Taiwan.|Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 404, Taiwan.
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Hsieh
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua, 500, Taiwan.
authors.forename: Mu-Kuan
authors.initials: MK
authors.lastname: Chen
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D036701:Limonins / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms
chemical_list: D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D036701:Limonins; C042198:nimbolide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020169:Caspases
keywords: MAPK; apoptosis; cell cycle; nasopharyngeal carcinoma; nimbolide