Tryptanthrin derivative CY-1-4 nanoparticle induces ferroptosis in B16-F10 cells
10.16438/j.0513-4870.2019-0200
- VernacularTitle:纳米化色胺酮类化合物CY-1-4诱导B16-F10细胞发生铁死亡
- Author:
Can-yu YANG
1
;
Da-kuan WANG
1
;
Hai-liang DENG
1
;
Hua ZHANG
1
;
Wen-bing DAI
1
;
Bing HE
1
;
Qiang ZHANG
1
,
2
;
Xiang-bao MENG
3
;
Xue-qing WANG
1
Author Information
1. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems
2. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
3. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
- Publication Type:Research Article
- Keywords:
tryptanthrin derivative CY-1-4;
nanoparticle;
melanoma;
cell death mechanism;
ferroptosis
- From:
Acta Pharmaceutica Sinica
2019;54(7):1288-1296
- CountryChina
- Language:Chinese
-
Abstract:
CY-1-4 is a tryptanthrin derivative exhibiting antitumor activity. The solubility of CY-1-4 was poor and the corresponding mechanism needs further study. To solve this problem, we prepared nanoparticles encapsulated with CY-1-4 (CY-1-4 NPs) by nanoprecipitation method using poly(caprolactone) (PCL) and poly(ethylene glycol)-co-poly(ε-caprolactone) (PEG-PCL) as carriers to improve solubility. We then explored whether CY-1-4 NPs induced B16-F10 cytotoxicity via ferroptosis by determining the effect of CY-1-4 NPs on reactive oxygen (ROS) levels, repairing efficacy of lipid reactive oxygen inhibitor ferrostatin-1 and iron chelator deferoxamine (DFO), and potentiation of protoporphyrin (PPIX) induced B16-F10 cell death. The results showed that nanoparticlated strategy significantly improved solubility of CY-1-4. With the particle size about 116 nm, encapsulating efficacy was about 83% and the drug loading capacity was about 4.80%. Ferroptosis mechanistic studies indicated that CY-1-4 NPs could improve the ROS level in B16-F10 cells, whereas ferrostatin-1 and DFO could partly inhibited the cytotoxicity and PPIX could potentiated the cytotoxicity of CY-1-4 NPs in B16-F10 cells. These results showed that ferroptosis was one of the cell death mechanisms induced by tryptanthrin derivative CY-1-4 nanoparticle.
