文献类型：期刊文献

英文题名：DMC triggers MDA-MB-231 cells apoptosis via inhibiting protective autophagy and PI3K/AKT/mTOR pathway by enhancing ROS level

作者：Jiang, Yu[1];Xu, Sunjie[1];Guo, Miaomiao[2];Lu, Zhi[3];Wei, Xing[1];An, Faliang[1,4];Xin, Xiujuan[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Beijing Technol & Business Univ, Key Lab Cosmet, China Natl Light Ind, 11-33 Fucheng Rd, Beijing 100048, Peoples R China;[3]Shanghai Inoherb Cosmet Co Ltd, Technol Ctr, 121 Chengyin Rd, Shanghai 200083, Peoples R China;[4]Marine Biomed Sci & Technol Innovat Platform Linga, 4 Lane 218,Haiji Sixth Rd, Shanghai 201306, Peoples R China

年份：2024

卷号：97

外文期刊名：TOXICOLOGY IN VITRO

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001224430400001)】；

基金：The National Natural Science Foundation of China funded this work. (Nos. 41876189, 81703388) . This work was also supported by the Open Research Fund Program of Key Laboratory of Cosmetic (Beijing Tech- nology and Business University) , China National Light Industry (KLC- 2022-YB3) .

语种：英文

外文关键词：DMC; MDA-MB-231 cells; Apoptosis; PI3K-AKT-mTOR pathway

摘要：DMC, a kind of compound derived from the dry flower buds of Cleistocalyx operculatus, has been shown to inhibit the growth of various cancer cells, but research on triple-negative breast cancer cells remains scarce. To explore this issue, MDA-MB-231 cells were selected, and the results showed that DMC has strong proliferation inhibit effects on this kind of cells. The inhibit rate of 30 mu M DMC incubated for 24 h was 56.25%, and 40.6% cells were arrested under the G2/M phase. The levels of pro-apoptosis protein Bax and active caspase-3, cleaved PARP and cell cycle related proteins, such as p21 and p27 increased, but apoptosis regulators, like Bcl-2, Cdc 2, Cyclin B1, and LC3 II decreased dramatically. In addition, DMC induced the accumulation of autophagosomes and autophagic substrates, and the combination of DMC with CQ promoted apoptosis of MDA-MB-231 cells, which suggested that DMC induced apoptosis partly by blocking autophagy flow. Moreover, the phosphorylation levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and its mechanistic target of rapamycin kinase (mTOR) were also decreased after 30 mu M DMC incubating for 24 h. The proteins play a critical role in cell proliferation, apoptosis, and autophagy modulation. The inhibition of autophagy flow and PI3K/AKT/mTOR pathway could be reversed after being treated with ROS scavenger NAC. Altogether, the results of the present study suggest that DMC effectively induces apoptosis and growth inhibition in MDA-MB-231 cells through blocking autophagy flow and regulating the PI3K/AKT/mTOR pathway by increasing ROS level.