The efficacy and mechanism of apoptosis induction by hypericin-mediated sonodynamic therapy in THP-1 macrophages

• DOI: 10.2147/ijn.s75398
• Publication Date: 2015-01-23T01:01:33Z
• Authors: Liming Yang; Xuesong Li; Lei Gao; Longbin Zheng; Jiayuan Kou; Xing Zhu; Yueqing Jiang; Zhaoyu Zhong; Juhua Dan; Haobo Xu; Yang Yang; Hong Li; Wenwu Cao; Yajun Zhao; Ye Tian; Sa Shi
• Keywords: Hypericin; Sonodynamic therapy; Propidium iodide; Viability assay; THP1 cell line

To investigate the sonoactivity of hypericin (HY), together with its sonodynamic effect on THP-1 macrophages and underlying mechanism.CCK-8 was used to examine cell viability. Confocal laser scanning microscopy performed assess localization HY in cells, reactive oxygen species (ROS) generation, opening mitochondrial permeability transition pore (mPTP) after different treatments. Apoptosis analyzed using Hoechst-propidium iodide transmission electron microscopy. Mitochondrial membrane potential (ΔΨm) collapse detected via fluorescence Lipoprotein oxidation determined malondialdehyde (MDA) assays. Western blotting conducted determine translocation BAX cytochrome C expression apoptosis-related proteins.HY sublocalized among nuclei mitochondria, endoplasmic reticulum, Golgi apparatus, lysosome cytosol macrophages. Under low-intensity ultrasound irradiation, significantly decreased viability induced apoptosis. Furthermore, greater ROS higher MDA levels, ΔΨm loss were observed therapy (SDT) group. Both generation levels reduced by scavenger N-acetyl cysteine (NAC) singlet sodium azide. Most inhibited pretreatment NAC, azide, mPTP inhibitor cyclosporin A (CsA). upon SDT but bongkrekic acid, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium, CsA, NAC. blot analyses revealed C, downregulated Bcl-2, upregulated cleaved caspase-9, caspase-3, poly(ADP-ribose) polymerase group, which reversed NAC.HY mediated SDT-induced apoptosis generation. Then, proapoptotic factor translocated from increasing ratio BAX/Bcl-2, opened release C. This study demonstrated great HY-mediated for treating atherosclerosis.