Synthesis and Antitumor Activities of Novel Mitochondria-Targeted Dihydroartemisinin Ether Derivatives.
Cangcang XuLinfan XiaoPeiyu LinXiyue YangXin ZouLingli MuXiaoping YangPublished in: ACS omega (2022)
Ten novel mitochondria-targeted dihydroartemisinin ether derivatives were designed, synthesized, and evaluated for antitumor activity against five cancer cell lines in vitro. Profoundly, compound D8-T (IC 50 = 56.9 nM) showed the most potent antiproliferative activity against the T24 cells with low cytotoxicity in normal human umbilical vein endothelial cells. High-performance liquid chromatography analysis confirmed that D8-T targeted mitochondria 6.3-fold higher than DHA. ATP content assay demonstrated that D8-T decreased the ATP level of bladder cancer cells. The effect of D8-T on cell apoptosis was determined by flow cytometry and western blot of Bax and Bcl-2. Surprisingly, the results indicated that D8-T did not induce bladder cancer cell apoptosis. In contrast, the cell cycle analysis and western blot of CDK4, CDK6, cyclin D1, and p21 demonstrated that the cancer cell cycle was arrested at the G1 phase after D8-T treatment. Furthermore, the consistent results were received by RNA-seq assay. These promising findings implied that D8-T could serve as a great candidate against bladder cancer for further investigation.
Keyphrases
- cell cycle
- cell proliferation
- rna seq
- high performance liquid chromatography
- flow cytometry
- papillary thyroid
- endothelial cells
- cancer therapy
- single cell
- cell death
- high throughput
- reactive oxygen species
- magnetic resonance
- mass spectrometry
- tandem mass spectrometry
- photodynamic therapy
- computed tomography
- simultaneous determination
- signaling pathway
- pi k akt
- ms ms
- high resolution
- young adults
- structure activity relationship
- endoplasmic reticulum stress
- lymph node metastasis
- replacement therapy
- vascular endothelial growth factor