Involvement of mitochondrial and reactive oxygen species in the sonodynamic toxicity of chlorin e6 in human leukemia K562 cells.
It is well accepted that sonodynamic therapy (SDT) exerts cytotoxicity and anti-tumor activity in many human tumors through the induction of cell apoptosis. The aim of the work described here was to study the effect of chlorin e6 (Ce6)-mediated SDT on human chronic myelogenous leukemia K562 cells. Our results indicate that Ce6-mediated SDT can suppress the viability of K562 cells. SDT caused apoptosis as analyzed by annexin V-phycoerythrin/7-amino-actinomycin D staining as well as cleavage of caspase 3 and the polypeptide poly(ADP-ribose) polymerase. After SDT exposure, loss of mitochondrial membrane potential, translocation of Bax from cytoplasm to mitochondria and activation of caspase 9 indicated that the mitochondrial-related apoptotic pathway might be activated. This process was accompanied by rapid generation of reactive oxygen species (ROS). Scavenging of ROS significantly blocked caspase-3 expression and the killing effect of SDT on K562 cells. Stress-activated protein kinases c-jun NH2-terminal kinase (JNK) and the p38 mitogen-activated protein kinase were activated after SDT treatment. Together, these findings indicate that Ce6-mediated SDT triggers mitochondria- and caspase-dependent apoptosis; oxidative injury may play a vital role in apoptotic signaling cascades.
Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Shaanxi, China.
Yixiang
Y
Li
Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Shaanxi, China. Electronic address: wangpan@snnu.edu.cn.
Pan
P
Wang
Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Shaanxi, China.
Xiaobing
X
Wang
Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Shaanxi, China.
Xiaomin
X
Su
Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest of China, College of Life Sciences, Shaanxi Normal University, Shaanxi, China. Electronic address: lshaof@snnu.edu.cn.
Quanhong
Q
Liu
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western / Q000379:methods; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002735:Chlorophyllides; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods; D011166:Porphyrins / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014464:Ultrasonic Therapy / Q000379:methods*
D002735:Chlorophyllides; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; C062985:phytochlorin; D053148:Caspase 3
Apoptosis; Chlorin e6; Mitochondria; Reactive oxygen species; Sonodynamic therapy