Caffeic Acid Phenethyl Ester Inhibits Ubiquitination and Degradation of p53 and Blocks Cervical Cancer Cell Growth
Caffeic Acid Phenethyl Ester Inhibits Ubiquitination and Degradation of p53 and Blocks Cervical Cancer Cell Growth
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DOI：
10.2174/1566524023666220829154716
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发表时间：
2023-01-01
影响因子：
2.5
通讯作者：
Wang, Chengcheng
中科院分区：
文献类型：
--
作者：
Li, Wei;Yang, Cong;Wang, Chengcheng
背景：在高危人乳头瘤病毒（HR-HPV）阳性的宫颈癌中，E3泛素连接酶e6相关蛋白（E6AP）介导肿瘤抑制因子p53的泛素化和蛋白酶体降解。本文研究了主要来源于蜂胶的天然产物咖啡酸苯乙酯（CAPE）是否能破坏E6AP与p53的相互作用，抑制p53的泛素化降解，并表现出抗宫颈癌的活性。方法采用CCK-8法、集落形成法和TUNEL法观察CAPE对hr - hpv阳性宫颈癌细胞株的抑制生长和诱导凋亡的作用。western blotting检测细胞凋亡相关蛋白。通过共免疫沉淀、泛素化实验和蛋白稳定性实验来确定CAPE是否可以破坏E6AP-p53相互作用并抑制p53的泛素化降解。结果CAPE可抑制hr - hpv阳性宫颈癌细胞的生长，并诱导凋亡相关通路的激活。重要的是，CAPE抑制E6AP表达并破坏E6AP与p53之间的相互作用。它抑制p53的泛素化并促进其稳定。结论CAPE对hpv阳性恶性细胞有治疗作用，临床应用有待进一步研究。
Background In high-risk human papillomavirus (HR-HPV)-positive cervical cancer, E6-associated protein (E6AP), an E3 ubiquitin ligase, mediates the ubiquitination and proteasomal degradation of the tumor suppressor p53. Here, we addressed the question of whether caffeic acid phenethyl ester (CAPE), a natural product mainly derived from propolis, can disrupt the interaction between E6AP and p53, inhibit ubiquitination degradation of p53 and exhibit anti-cervical cancer activity.Methods The ability of CAPE to inhibit growth and to induce apoptosis was shown in HR-HPV-positive cervical cancer cell lines by performing CCK-8, colony formation and TUNEL assays. Apoptosis-related proteins were tested by western blotting. Coimmunoprecipitation, ubiquitination assay and protein stability assay were carried out to determine whether CAPE can disrupt the E6AP-p53 interaction and inhibit ubiquitination degradation of p53.Results Our results showed that CAPE inhibits the growth of HR-HPV-positive cervical cancer cells and induces the activation of apoptosis-related pathways. Importantly, CAPE inhibits E6AP expression and disrupts the interaction between E6AP and p53. It inhibits the ubiquitination of p53 and promotes its stabilization.Conclusion In summary, CAPE has a therapeutic effect on HPV-positive malignant cells, so further studies are needed to assess its clinical application.