title: Sonodynamically induced anti-tumor effect of 5-aminolevulinic acid on pancreatic cancer cells.
abstract: Sonodynamic therapy (SDT), a promising modality for cancer treatment, involves the synergistic interaction of ultrasound and some chemical compounds termed sonosensitizers. However, its effect on pancreatic cancer cells remains unclear. In our study, we sought to identify the cytotoxic effects of ultrasound-activated 5-aminolevulinic acid on human pancreatic cancer Capan-1 cells. Cell viability was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) analysis; mitochondrial membrane potential was assessed using the fluorescent probe jc-1; apoptosis was evaluated by flow cytometry; cell morphology was investigated by scanning electron microscopy; apoptosis-related protein expression was analyzed by Western blot assay. We found that SDT significantly decreased the survival rate of cells, and this effect increased with 5-aminolevulinic acid concentration and ultrasound exposure time. The mechanism underlying the effect of SDT involves, in part, the induction of a conspicuous loss in mitochondrial membrane potential and, in part, the induction of apoptosis through upregulation of Bax expression, downregulation of Bcl-2 and increased activation of procaspase-3. These results indicate that the ultrasonically induced cell killing effect could be enhanced by 5-ALA and that the mitochondrial pathway might be involved in the cell damage process. We conclude that SDT is a promising new methodology for pancreatic cancer treatment.
authors.affiliation: Department of Gastrointestinal Oncology, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Yan Jing
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Oncology, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Gastrointestinal Oncology, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Cai Ling
authors.initials: CL
authors.lastname: Jiang
authors.affiliation: Department of Gastrointestinal Oncology, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: De Xin
authors.initials: de X
authors.lastname: Jia
authors.affiliation: Department of Gastrointestinal Oncology, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Xiao Xue
authors.initials: XX
authors.lastname: Du
authors.affiliation: Department of Gastrointestinal Oncology, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Jian Hua
authors.initials: JH
authors.lastname: Zhou
authors.affiliation: Department of Gastrointestinal Oncology, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Gastrointestinal Oncology, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Sui
authors.affiliation: Department of Gastrointestinal Oncology, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Xiao Li
authors.initials: XL
authors.lastname: Wei
authors.affiliation: Department of Gastrointestinal Oncology, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal Oncology, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Heng Heng
authors.initials: HH
authors.lastname: Yuan
authors.affiliation: Department of Gastrointestinal Oncology, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Ting Ting
authors.initials: TT
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Oncology, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Wen Jie
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Oncology, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xie
authors.affiliation: Department of Gastrointestinal Oncology, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Xiao Hui
authors.initials: XH
authors.lastname: Lang
authors.affiliation: Department of Gastrointestinal Oncology, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Li Ying
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Oncology, Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal Oncology, Third Affiliated Hospital, Harbin Medical University, Harbin, China. Electronic address: Bai_yuxian@126.com.
authors.forename: Yu Xian
authors.initials: YX
authors.lastname: Bai
authors.affiliation: Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, China. Electronic address: yetian@ems.hrbmu.edu.cn.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
mesh_terms: D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D010190:Pancreatic Neoplasms / Q000628:therapy*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid
keywords: 5-Aminolevulinic acid; Apoptosis; Mitochondria; Sonodynamic therapy