Nimbolide induces apoptosis in human nasopharyngeal cancer cells

• Published in: Environmental toxicology 2017-08, Vol.32 (8), p.2085-2092
• Main Authors: Chien, Su‐Yu, Hsu, Ching‐Hui, Lin, Chia‐Chieh, Chuang, Yi‐Ching, Lo, Yu‐Sheng, Hsi, Yi‐Ting, Hsieh, Ming‐Ju, Chen, Mu‐Kuan
• Format: Article
• Language: English
• Subjects: Adenosine diphosphate; ADP; Anti-Inflammatory Agents - pharmacology; Anticancer properties; Antineoplastic Agents, Phytogenic - pharmacology; Antitumor activity; Antitumour agents; Apoptosis; Apoptosis - drug effects; Cancer; Carcinoma; Caspase; Caspase-3; Caspases - metabolism; Cell cycle; Cell Cycle Checkpoints; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemotherapy; Diagnostic systems; Epithelial cells; Extracellular; Extracellular signal-regulated kinase; Humans; Inflammation; Kinases; Limonins - pharmacology; Malignancy; MAP Kinase Signaling System; MAPK; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Modulation; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Nasopharynx; Neoplasms; nimbolide; Proliferation; Ribose; Sensitivity enhancement; Throat cancer
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.22423

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.