活性氧
细胞凋亡
人体乳房
药品
癌症研究
化学
癌细胞
癌症
药理学
生物
医学
生物化学
内科学
作者
Na Young Kim,Dukanya Dukanya,Gautam Sethi,Swamy Savvemala Girimanchanaika,Ji-Rui Yang,O. Nagaraja,S. Ananda,Divakar Vishwanath,Keerthikumara Venkantesha,Shreeja Basappa,Arunachalam Chinnathambi,Sulaiman Ali Alharbi,M. Mahendra,Alexey Yu. Sukhorukov,Vijay Pandey,Peter E. Lobie,Basappa Basappa,Kwang Seok Ahn
标识
DOI:10.1016/j.tranon.2024.102101
摘要
Small molecule-driven JNK activation has been found to induce apoptosis and paraptosis in cancer cells. Herein pharmacological effects of synthetic oxazine (4aS, 7aS)-3-((4-(4‑chloro-2-fluorophenyl)piperazin-1-yl)methyl)-4-phenyl-4, 4a, 5, 6, 7, 7a-hexahydrocyclopenta[e] [1,2]oxazine (FPPO; BSO-07) on JNK-driven apoptosis and paraptosis has been demonstrated in human breast cancer (BC) MDA-MB231 and MCF-7 cells respectively. BSO-07 imparted significant cytotoxicity in BC cells, induced activation of JNK, and increased intracellular reactive oxygen species (ROS) levels. It also enhanced the expression of apoptosis-associated proteins like PARP, Bax, and phosphorylated p53, while decreasing the levels of Bcl-2, Bcl-xL, and Survivin. Furthermore, the drug altered the expression of proteins linked to paraptosis, such as ATF4 and CHOP. Treatment with N-acetyl-cysteine (antioxidant) or SP600125 (JNK inhibitor) partly reversed the effects of BSO-07 on apoptosis and paraptosis. Advanced in silico bioinformatics, cheminformatics, density Fourier transform and molecular electrostatic potential analysis further demonstrated that BSO-07 induced apoptosis and paraptosis via the ROS/JNK pathway in human BC cells.
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