ROS generation attenuates the anti-cancer effect of CPX on cervical cancer cells by inducing autophagy and inhibiting glycophagy.
ROS generation attenuates the anti-cancer effect of CPX on cervical cancer cells by inducing autophagy and inhibiting glycophagy.
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ROS的产生通过诱导自噬和抑制糖噬减弱CPX对宫颈癌细胞的抗癌作用
DOI：
10.1016/j.redox.2022.102339
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发表时间：
2022-07
期刊：
影响因子：
11.4
通讯作者：
Lei, Yunlong
中科院分区：
文献类型：
--
作者：
Fan, Hui;He, Yujia;Xiang, Junqi;Zhou, Jing;Wan, Xinyan;You, Jiawei;Du, Kailong;Li, Yue;Cui, Lin;Wang, Yitao;Zhang, Chundong;Bu, Youquan;Lei, Yunlong
宫颈癌是妇科最常见的恶性肿瘤之一，由于化疗耐药和反复复发，预后差。环吡酮胺（CPX）是一种人工合成的抗真菌药物，最近被发现是一种很有前途的抗癌药物。然而，与其抗癌作用相关的详细机制仍不清楚，需要进一步阐明。在这项研究中，我们发现CPX可以通过靶向PARK 7诱导宫颈癌细胞的增殖抑制。进一步的结果表明，CPX可以通过下调PARK 7的表达来激活PRKAA 1或通过PARK 7非依赖性的ROS积累来抑制mTOR信号传导，从而诱导细胞保护性自噬。同时，CPX处理增加了宫颈癌细胞的糖原聚集和糖噬。活性氧清除剂N-乙酰基-l-半胱氨酸（NAC）的存在通过减少自噬和增强糖噬，导致细胞中糖原进一步聚集，从而促进CPX诱导的对宫颈癌细胞增殖的抑制。总之，我们的研究为CPX在抗癌治疗中的分子机制提供了新的见解，并为癌症治疗中的糖噬开辟了新的途径。CPX通过靶向PARK 7诱导细胞保护性自噬并抑制宫颈癌细胞增殖ROS的产生通过诱导细胞保护性自噬和抑制糖噬来减弱CPX的抗癌作用。ROS触发的糖原聚集和YAP 1的失活参与了CPX的抗癌作用。
Cervical cancer is one of the most common gynecological malignancies with poor prognosis due to constant chemoresistance and repeated relapse. Ciclopirox olamine (CPX), a synthetic antifungal agent, has recently been identified to be a promising anti-cancer candidate. However, the detailed mechanisms related to its anti-cancer effects remain unclear and need to be further elucidated. In this study, we found that CPX could induce proliferation inhibition in cervical cancer cells by targeting PARK7. Further results demonstrated that CPX could induce cytoprotective autophagy by downregulating the expression of PARK7 to activate PRKAA1 or by PARK7-independent accumulation of ROS to inhibit mTOR signaling. Meanwhile, CPX treatment increased the glycogen clustering and glycophagy in cervical cancer cells. The presence of N-acetyl-l-cysteine (NAC), a ROS scavenger, led to further clustering of glycogen in cells by reducing autophagy and enhancing glycophagy, which promoted CPX-induced inhibition of cervical cancer cell proliferation. Together, our study provides new insights into the molecular mechanisms of CPX in the anti-cancer therapy and opens new avenues for the glycophagy in cancer therapeutics. CPX induces cytoprotective autophagy and inhibits proliferation of cervical cancer cells by targeting PARK7. ROS generation attenuates the anticancer effect of CPX by inducing cytoprotective autophagy and inhibiting glycophagy. ROS-triggered glycogen clustering and inactivation of YAP1 are involved in the anti-cancer effects of CPX.
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影响因子：
6.4
作者：
Braun, Julia A.;Herrmann, Anja L.;Hoppe-Seyler, Felix
通讯作者：
Hoppe-Seyler, Felix
DOI：
10.1073/pnas.0607260103
发表时间：
2006-10-10
影响因子：
11.1
作者：
Clements, Casey M.;McNally, Richard S.;Ting, Jenny P-Y.
通讯作者：
Ting, Jenny P-Y.
影响因子：
5.3
作者：
Bjorkblom, Benny;Maple-Grodem, Jodi;Moller, Simon Geir
通讯作者：
Moller, Simon Geir
影响因子：
2
作者：
Arnouk, Hilal;Merkley, Mark A.;Podolsky, Robert H.;Stoeppler, Hubert;Santos, Carlos;Alvarez, Manuel;Mariategui, Julio;Ferris, Daron;Lee, Jeffrey R.;Dynan, William S.
通讯作者：
Dynan, William S.
影响因子：
20.3
作者：
Auberger, Patrick;Puissant, Alexandre
通讯作者：
Puissant, Alexandre