title: Sonodynamic action of hypocrellin B triggers cell apoptoisis of breast cancer cells involving caspase pathway.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an, China; School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an, China.
authors.forename: Quanhong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Albert Wingnang
authors.initials: AW
authors.lastname: Leung
authors.affiliation: Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Xi'an, China; School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China. Electronic address: wangpan@snnu.edu.cn.
authors.forename: Pan
authors.initials: P
authors.lastname: Wang
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China. Electronic address: xcshan@163.com.
authors.forename: Chuanshan
authors.initials: C
authors.lastname: Xu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D020169:Caspases; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011809:Quinones / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D017319:Photosensitizing Agents; D011809:Quinones; D017382:Reactive Oxygen Species; D010569:Perylene; D020169:Caspases; C064522:hypocrellin B
keywords: Apoptosis; Breast cancer cells; Caspase pathway; Hypocrellin B; Mitochondrial damage; Sonodynamic therapy