期刊
LIFE-BASEL
卷 12, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/life12050687
关键词
apoptosis; topoisomerase; reactive oxygen species (ROS); heat shock protein 90 (HSP90); aeroplysinin-1 (Apl-1); NADPH oxidases (NOXs)
资金
- Ministry of Science and Technology [MOST 110-2320B-259-001-MY3, 110-2314-B-037-083]
- National Health Research Institutes [NHRI-110A1-CACO-03212109]
- National Dong Hwa University [111T2560-5]
Aeroplysinin-1 exhibits cytotoxicity against leukemia and prostate cancer cells through multiple pathways.
Aeroplysinin-1 is a brominated isoxazoline alkaloid that has exhibited a potent antitumor cell effect in previous reports. We evaluated the cytotoxicity of aeroplysinin-1 against leukemia and prostate cancer cells in vitro. This marine alkaloid inhibited the cell proliferation of leukemia Molt-4, K562 cells, and prostate cancer cells Du145 and PC-3 with IC50 values of 0.12 +/- 0.002, 0.54 +/- 0.085, 0.58 +/- 0.109 and 0.33 +/- 0.042 mu M, respectively, as shown by the MTT assay. Furthermore, in the non-malignant cells, CCD966SK and NR8383, its IC50 values were 1.54 +/- 0.138 and 6.77 +/- 0.190 mu M, respectively. In a cell-free system, the thermal shift assay and Western blot assay verified the binding affinity of aeroplysinin-1 to Hsp90 and Topo II alpha, which inhibited their activity. Flow cytometry analysis showed that the cytotoxic effect of aeroplysinin-1 is mediated through mitochondria-dependent apoptosis induced by reactive oxygen species (ROS). ROS interrupted the cellular oxidative balance by activating NOX and inhibiting HIF-1 alpha and HO-1 expression. Pretreatment with N-acetylcysteine (NAC) reduced Apl-1-induced mitochondria-dependent apoptosis and preserved the expression of NOX, HO-1, and HIF-1a. Our findings indicated that aeroplysinin-1 targeted leukemia and prostate cancer cells through multiple pathways, suggesting its potential application as an anti-leukemia and prostate cancer drug lead.
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