4.7 Article

Ursolic acid enhances the antitumor effects of sorafenib associated with Mcl-1-related apoptosis and SLC7A11-dependent ferroptosis in human cancer

期刊

PHARMACOLOGICAL RESEARCH
卷 182, 期 -, 页码 -

出版社

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2022.106306

关键词

Sorafenib; Ursolic acid; Apoptosis; Ferroptosis; Cancer

资金

  1. National Science Fund of China-Science and Technology Development Fund of Macau SAR [32161160303, 0010/2021/AFJ]
  2. Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University [ZNJC201933]
  3. Key Project of Guangzhou Municipal Science and Technology Bureau [201903010039]

向作者/读者索取更多资源

The combination of sorafenib and ursolic acid has shown significant synergistic antitumor activity in both in vitro and in vivo tumor xenograft models. The treatment induces selective apoptotic death and ferroptosis in cancer cells through the accumulation of intracellular reactive oxygen species. These findings suggest a novel effective therapeutic strategy for tumor treatment.
As a broad-spectrum oral small molecule inhibitor targeting multikinase, sorafenib is currently approved for the clinical treatment of several types of cancer as a single agent. A considerable number of clinical trial results have indicated that combination therapies involving sorafenib have been shown to improve treatment efficacy and may lead to novel therapeutic applications. Ursolic acid (UA), a natural pentacyclic triterpene compound extracted from a great variety of traditional medicinal plants and most fruits and vegetables, exhibits a wide range of therapeutic potential, including against cancer, diabetes, brain disease, liver disease, cardiovascular diseases, and sarcopenia. In the present study, we investigated the antitumor effects of sorafenib in combination with ursolic acid and found that the two agents displayed significant synergistic antitumor activity in in vitro and in vivo tumor xenograft models. Sorafenib/UA induced selective apoptotic death and fermptosis in various cancer cells by evoking a dramatic accumulation of intracellular lipid reactive oxygen species (ROS). Mechanistically, the combination treatment promoted Mcl-1 degradation, which regulates apoptosis. However, decreasing the protein level of SLC7A11 plays a critical role in sorafenib/UA-induced cell fermptosis. Therefore, these results suggest that the synergistic antitumor effects of sorafenib combined with ursolic acid may involve the induction of Mcl-1-related apoptosis and SLC7A11-dependent ferroptosis. Our findings may offer a novel effective therapeutic strategy for tumor treatment.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据