Chen Jian, Zhang Linlin, Shu Yilai, Chen Liping, Zhu Min, Yao Song, Wang Jiabing, Wu Jianzhang, Liang Guang, Wu Haitao, Li Wulan
Departments of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.
Chemical Biology Research Center, College of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Biomed Res Int. 2017;2017:4751260. doi: 10.1155/2017/4751260. Epub 2017 Mar 20.
Laryngeal carcinoma remains one of the most common malignancies, and curcumin has been proven to be effective against head and neck cancers in vitro. However, it has not yet been applied in clinical settings due to its low stability. In the current study, we synthesized 34 monocarbonyl analogues of curcumin with stable structures. CA15, which exhibited a stronger inhibited effect on laryngeal cancer cells HEp-2 but a lower toxicity on hepatic cells HL-7702 in MTT assay, was selected for further analysis. The effects of CA15 on cell viability, proliferation, migration, apoptosis, and NF-B activation were measured using MTT, Transwell migration, flow cytometry, Western blot, and immunofluorescence assays in HEp-2 cells. An NF-B inhibitor, BMS-345541, as well as curcumin was also tested. Results showed that CA15 induced decreased toxicity towards HL-7702 cells compared to curcumin and BMS-345541. However, similar to BMS-345541 and curcumin, CA15 not only significantly inhibited proliferation and migration and induced caspase-3-dependent apoptosis but also attenuated TNF--induced NF-B activation in HEp-2 cells. These results demonstrated that curcumin analogue CA15 exhibited anticancer effects on laryngeal cancer cells via targeting of NF-B.
喉癌仍然是最常见的恶性肿瘤之一,姜黄素已被证明在体外对头颈癌有效。然而,由于其稳定性低,尚未应用于临床。在本研究中,我们合成了34种结构稳定的姜黄素单羰基类似物。在MTT试验中,对喉癌细胞HEp-2表现出较强抑制作用且对肝细胞HL-7702毒性较低的CA15被选作进一步分析。使用MTT、Transwell迁移、流式细胞术、蛋白质免疫印迹和免疫荧光试验检测CA15对HEp-2细胞活力、增殖、迁移、凋亡和NF-κB激活的影响。还测试了一种NF-κB抑制剂BMS-345541以及姜黄素。结果表明,与姜黄素和BMS-345541相比,CA15对HL-7702细胞的毒性降低。然而,与BMS-345541和姜黄素类似,CA15不仅显著抑制增殖和迁移并诱导caspase-3依赖性凋亡,还减弱了肿瘤坏死因子-α诱导的HEp-2细胞中NF-κB的激活。这些结果表明,姜黄素类似物CA15通过靶向NF-κB对喉癌细胞表现出抗癌作用。