双氢青蒿素
癌细胞
线粒体
毒性
癌症
癌症研究
线粒体毒性
细胞生长
药理学
生物
化学
细胞生物学
生物化学
免疫学
青蒿素
遗传学
有机化学
疟疾
恶性疟原虫
作者
Mahboubeh Varmazyad,Mira M. Modi,Amanda L. Kalen,Ehab H. Sarsour,Brett A. Wagner,Juan Du,Michael Schultz,Garry R. Buettner,F. Christopher Pigge,Prabhat C. Goswami
标识
DOI:10.1016/j.freeradbiomed.2021.01.050
摘要
Dihydroartemisinin (DHA) is an FDA-approved antimalarial drug that has been repurposed for cancer therapy because of its preferential antiproliferative effects on cancer versus normal cells. Mitochondria represent an attractive target for cancer therapy based on their regulatory role in proliferation and cell death. This study investigates whether DHA conjugated to innately fluorescent N-alkyl triphenylvinylpyridinium (TPVP) perturbs mitochondrial functions resulting in a differential toxicity of cancer versus normal cells. TPVP-DHA treatments resulted in a dose-dependent toxicity of human melanoma and pancreatic cancer cells, whereas normal human fibroblasts were resistant to this treatment. TPVP-DHA treatments resulted in a G1-delay of the cancer cell cycle, which was also associated with a significant inhibition of the mTOR-metabolic and ERK1/2-proliferative signaling pathways. TPVP-DHA treatments perturbed mitochondrial functions, which correlated with increases in mitochondrial fission. In summary, TPVP mediated mitochondrial targeting of DHA enhanced cancer cell toxicity by perturbing mitochondrial functions and morphology.
科研通智能强力驱动
Strongly Powered by AbleSci AI