Autophagy Induced by Areca Nut Extract Contributes to Decreasing Cisplatin Toxicity in Oral Squamous Cell Carcinoma Cells: Roles of Reactive Oxygen Species/AMPK Signaling.
Autophagy Induced by Areca Nut Extract Contributes to Decreasing Cisplatin Toxicity in Oral Squamous Cell Carcinoma Cells: Roles of Reactive Oxygen Species/AMPK Signaling.
复制标题
槟榔提取物诱导的自噬有助于降低口腔鳞状细胞癌细胞中的顺铂毒性：活性氧/AMPK 信号传导的作用
DOI：
10.3390/ijms18030524
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发表时间：
2017-03-01
影响因子：
5.6
通讯作者：
Shang ZJ
中科院分区：
文献类型：
--
作者：
Xu Z;Huang CM;Shao Z;Zhao XP;Wang M;Yan TL;Zhou XC;Jiang EH;Liu K;Shang ZJ
咀嚼槟榔与口腔鳞状细胞癌（OSCC）密切相关。本研究旨在探讨槟榔提取物（ANE）与顺铂对口腔鳞癌细胞毒性之间的潜在关系。用ANE和/或顺铂处理后，分析OSCC细胞（Cal-27和Scc-9）的存活率和凋亡。对自噬相关蛋白和AMPK信号网络的表达进行了评价。我们发现，晚期口腔鳞癌患者咀嚼槟榔的习惯提出了较高的LC 3表达和预后较差。在ANE的长时间处理（6天，3 μg）后诱导活性氧（ROS）介导的自噬。ANE处理（6天，3 μg）后，顺铂毒性（IC 50，48 h）在OSCC细胞中降低。顺铂毒性可通过3-甲基腺嘌呤（3-MA）、N-乙酰基-L-半胱氨酸（NAC）或化合物C预处理逆转自噬而增强。在顺铂存在的情况下，ANE处理的OSCC细胞中切割的聚（ADP-核糖）聚合酶（cl-PARP）和切割的半胱天冬酶3（cl-caspase 3）下调，这也被NAC和化合物C逆转。ANE可通过诱导自噬来降低顺铂对OSCC的毒性作用，自噬过程涉及ROS和AMPK/mTOR信号通路。
Chewing areca nut is closely associated with oral squamous cell carcinoma (OSCC). The current study aimed to investigate potential associations between areca nut extract (ANE) and cisplatin toxicity in OSCC cells. OSCC cells (Cal-27 and Scc-9) viability and apoptosis were analyzed after treatment with ANE and/or cisplatin. The expressions of proteins associated with autophagy and the AMP-activated protein kinase (AMPK) signaling network were evaluated. We revealed that advanced OSCC patients with areca nut chewing habits presented higher LC3 expression and poorer prognosis. Reactive oxygen species (ROS)-mediated autophagy was induced after pro-longed treatment of ANE (six days, 3 μg). Cisplatin toxicity (IC50, 48 h) was decreased in OSCC cells after ANE treatment (six days, 3 μg). Cisplatin toxicity could be enhanced by reversed autophagy by pretreatment of 3-methyladenine (3-MA), N-acetyl-l-cysteine (NAC), or Compound C. Cleaved-Poly-(ADP-ribose) polymerase (cl-PARP) and cleaved-caspase 3 (cl-caspase 3) were downregulated in ANE-treated OSCC cells in the presence of cisplatin, which was also reversed by NAC and Compound C. Collectively, ANE could decrease cisplatin toxicity of OSCC by inducing autophagy, which involves the ROS and AMPK/mTOR signaling pathway.