Alkaloids from Piper nigrum Synergistically Enhanced the Effect of Paclitaxel against Paclitaxel-Resistant Cervical Cancer Cells through the Downregulation of Mcl-1
Alkaloids from Piper nigrum Synergistically Enhanced the Effect of Paclitaxel against Paclitaxel-Resistant Cervical Cancer Cells through the Downregulation of Mcl-1
复制标题
黑胡椒生物碱通过下调 Mcl-1 协同增强紫杉醇对抗紫杉醇耐药宫颈癌细胞的作用
DOI：
10.1021/acs.jafc.9b01320
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发表时间：
2019
影响因子：
6.1
通讯作者：
Jianqing Yu
中科院分区：
文献类型：
--
作者：
Zhoufan Xie;Yulu Wei;Jie Xu;Jiachuan Lei;Jianqing Yu
在当前的研究中，从黑胡椒中鉴定出九种酰胺生物碱，包括两种新的二聚酰胺和一种新的天然产物。其中，7种化合物使紫杉醇耐药的宫颈癌细胞HeLa/PTX对紫杉醇敏感。胡椒碱是从胡椒中提取的主要成分，并对其致敏机制进行了研究。联合治疗增强了细胞凋亡，这是由磷酸 Akt 和 Mcl-1 下调介导的。胡椒碱 (50 μM) 与紫杉醇 (200 nM) 联合下调 Mcl-1 蛋白表达，降低幅度为 35.9 ± 9.5% (P< 0.05)。此外，Mcl-1 的过度表达减弱了该组合的抑制作用。此外，六种二聚酰胺生物碱和紫杉醇的联合治疗均下调了Mcl-1蛋白的表达，降低范围为23.5±9.7%至41.7±7.2%（P<0.05）。我们首次揭示植物中的二聚酰胺生物碱对癌细胞对紫杉醇具有显着的增敏作用。
In the current study, nine amide alkaloids, including two new dimeric amides and a new natural product, were identified fromPiper nigrum. Among them, seven compounds sensitized paclitaxel-resistant cervical cancer cells HeLa/PTX to paclitaxel. Piperine was a major component obtained fromPiper nigrum, and its sensitization mechanism was investigated. Combination treatment enhanced cell apoptosis, which was mediated by downregulation of phospho-Akt and Mcl-1. Piperine (50 μM) combined with paclitaxel (200 nM) downregulated Mcl-1 protein expression with a decrease of 35.9 ± 9.5% (P< 0.05). Moreover, overexpression of Mcl-1 attenuated the inhibitory effect of this combination. Furthermore, combination treatments of six dimeric amide alkaloids and paclitaxel all downregulated Mcl-1 protein expression with a decrease ranging from 23.5 ± 9.7% to 41.7 ± 7.2% (P< 0.05). We reveal, for the first time, that dimeric amide alkaloids from plants possess a remarkable sensitization effect on cancer cells to paclitaxel.