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Oxazine drug-seed induces paraptosis and apoptosis through reactive oxygen species/JNK pathway in human breast cancer cellsстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Kim Na Young, Dukanya Dukanya, Sethi Gautam, Girimanchanaika Swamy S., Yang Jirui, Nagaraja Omantheswara, Swamynayaka Ananda, Vishwanath Divakar, Venkantesha Keerthikumara, Basappa Shreeja, Chinnathambi Arunachalam, Alharbi Sulaiman Ali, Madegowda Mahendra, Sukhorukov Alexey, Pandey Vijay, Lobie Peter E., Basappa Basappa, Ahn Kwang Seok
- Журнал: Translational Oncology
- Том: 49
- Год издания: 2024
- Издательство: Neoplasia Press
- Местоположение издательства: United States
- Номер статьи: 102101
- DOI: 10.1016/j.tranon.2024.102101
- Аннотация: 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.
- Добавил в систему: Сухоруков Алексей Юрьевич