Sonodynamic action of hypocrellin B triggers cell apoptoisis of breast cancer cells involving caspase pathway

Objectives: The aim of the present study is to investigate the effects of sonodynamic action of hypocrellin B on human breast cancer cells and further explore its underlying mechanisms. Methods: The cell viability of breast cancer MDA-MB-231 cells was examined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Alterations on cell apoptosis, intracellular reactive oxygen species generation (ROS), mitochondrial membrane potential, and DNA fragmentation was analyzed by flow cytometer. The subcellular localization of hypocrellin B was assessed by a confocal laser scanning microscope. Mitochondria damage and nuclear morphological changes were observed under a fluorescence microscope. To further explore whether caspase pathway was involved in cell apoptotic induction of sonodynamic action of hypocrellin B, the pan-caspase inhibitor Z-Val-Ala-DL-Asp (ome)Fluoromethylketone (z-VAD-fmk) was added to the cells one hour prior to loading the sonosensitizer, and then cell viability and apoptosis were analyzed after hypocrellin B treatment. Results: Sonodynamic treatment of hypocrellin B HB significantly suppressed cell viability of MDA-MB-231 cells. Sonodynamic action of hypocrellin B caused excessive ROS accumulation, mitochondrial dysfunction, cell apoptosis, DNA fragmentation and nuclear morphological damage. Moreover, the cytotoxicity and cell apoptosis induced by sonodynamic action of hypocrellin B were remarkably rescued by the caspase spectrum inhibitor z-VAD-fmk. Conclusions: These results demonstrated that hypocrellin B had significant sonodynamic killing and apoptotic induction effect on breast cancer cells. And cell apoptosis induced by sonodynamic action of hypocrellin B was partly dependent on caspase pathway. (C) 2016 Elsevier B.V. All rights reserved.