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印楝素诱导人鼻咽癌细胞凋亡。

Nimbolide induces apoptosis in human nasopharyngeal cancer cells.

作者信息

Chien Su-Yu, Hsu Ching-Hui, Lin Chia-Chieh, Chuang Yi-Ching, Lo Yu-Sheng, Hsi Yi-Ting, Hsieh Ming-Ju, Chen Mu-Kuan

机构信息

Department of Pharmacy, Changhua Christian Hospital, Changhua, 500, Taiwan.

College of Health Sciences, Chang Jung Christian University, Tainan, 71101, Taiwan.

出版信息

Environ Toxicol. 2017 Aug;32(8):2085-2092. doi: 10.1002/tox.22423. Epub 2017 Apr 6.

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.

摘要

鼻咽癌(NPC)是一种起源于覆盖鼻咽表面和内衬的上皮细胞的肿瘤,在全球范围内是一种罕见的恶性肿瘤,但在某些地理区域较为普遍,如南亚(台湾、香港、新加坡、马来西亚和中国南方)和北非。尽管诊断技术有所进步,治疗方式也有所改进,但鼻咽癌的预后仍然很差。因此,迫切需要一种有效的化疗方案来提高肿瘤对化疗药物的敏感性。印楝素(Nimbolide)源自印楝(Azadirachta indica),具有广泛的有益作用,包括抗炎和抗癌特性。本研究评估了印楝素在鼻咽癌细胞中的抗肿瘤活性及其潜在机制。我们的结果显示,用印楝素处理HONE-1细胞可有效抑制细胞活力。此外,印楝素导致细胞周期停滞,随后激活半胱天冬酶-3、-8和-9以及聚(ADP-核糖)聚合酶以诱导细胞凋亡。此外,印楝素诱导HONE-1细胞中Bik、Bax和t-Bid的表达。结果表明,印楝素通过调节细胞外信号调节激酶1和2(ERK1/2)途径诱导细胞凋亡。印楝素可诱导人鼻咽癌细胞凋亡,是一种潜在的预防鼻咽癌增殖的化学预防剂。©2016威利期刊公司。《环境毒理学》32: 2085 - 2092, 2017。

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