Curcumin analog, WZ37, promotes G2/M arrest and apoptosis of HNSCC cells through Akt/mTOR inhibition
Curcumin analog, WZ37, promotes G2/M arrest and apoptosis of HNSCC cells through Akt/mTOR inhibition
复制标题
姜黄素类似物 WZ37 通过 Akt/mTOR 抑制促进 HNSCC 细胞的 G2/M 期阻滞和凋亡
DOI：
10.1016/j.tiv.2019.104754
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发表时间：
2020-06-01
影响因子：
3.2
通讯作者：
Wang, Yi
中科院分区：
文献类型：
--
作者：
Zhang, Ziheng;Lin, Renyu;Wang, Yi
头颈部鳞状细胞癌（HNSCC）是头颈部恶性肿瘤的主要形式。现有的常规治疗方法对晚期HNSCC具有毒性和耐药性，因此迫切需要新的高效治疗药物。本研究研究了姜黄素类似物WZ37对HNSCC细胞的抗癌作用，并明确了其作用机制。结果表明，WZ37通过G2/M周期阻滞抑制几种HNSCC细胞类型的增殖，促进促凋亡蛋白谱的表达，诱导ros依赖性线粒体损伤和内质网应激。用活性氧清除剂NAC预处理可降低WZ37在HEP-2细胞中的抗癌活性。长期治疗WZ37 （24 h）可降低Akt/mTOR磷酸化水平，同时BAD和PTEN表达升高。此外，WZ37与MK-2206 （Akt抑制剂）共处理可促进癌细胞凋亡。我们的研究结果表明，WZ37的抗癌潜力归因于ros依赖的细胞周期阻滞、线粒体损伤和内质网应激，导致细胞凋亡。HNSCC细胞凋亡的基础机制是通过抑制氧化敏感的Akt/mTOR通路。我们认为WZ37可能是一种很有前景的治疗HNSCC的抗癌药物。
Head and neck squamous cell carcinoma (HNSCC) is a leading form of malignancy arising from the head and neck region. Existing conventional therapies are toxic and induce resistance to advanced HNSCC, therefore, new highly efficient therapeutic agents are urgently needed. The present study investigated the anti-cancer efficacy of WZ37, a curcumin analog, in HNSCC cell lines, and defined the mechanism of this activity. Results indicated that WZ37 inhibited proliferation of several HNSCC cell types by G2/M cycle arrest, promoted expression of a proapoptotic protein profile, and induced ROS-dependent mitochondrial injury and ER stress. Pre-treatment with NAC, an ROS scavenger, lowered the anti-cancer activity of WZ37 in HEP-2 cells. Long-term treatment of WZ37 (24 h) decreased Akt/mTOR phosphorylation which was accompanied by increased expression of BAD and PTEN. Moreover, co-treatment of WZ37 with MK-2206 (Akt inhibitor) promoted cancer cell apoptosis. Our findings indicated that the anti-cancer potential of WZ37 was attributed to ROS-dependent cell cycle arrest, mitochondrial injury, and ER stress, leading to apoptosis. The basis of the HNSCC cell apoptosis was through a mechanism of inhibition of the oxidant-sensitive Akt/mTOR pathway. We conclude that WZ37 can be a promising anti-cancer agent for the treatment of HNSCC.