title: Initiation of autophagy and apoptosis by sonodynamic therapy in murine leukemia L1210 cells.
abstract: Sonodynamic therapy (SDT) has shown great potential in target cancer therapy, but it induced cell death modes has not been fully investigated. This study was to examine autophagic and apoptotic responses to protoporphyrin IX (PpIX) mediated SDT in murine leukemia L1210 cells. After SDT, the occurrence of autophagy was identified by morphological observation and biochemical analysis. Meanwhile, the mitochondria dependent apoptosis pathway was examined to participate in SDT induced cell death. The relationship between autophagy and apoptosis was further investigated by applying pharmacological inhibition studies, which indicated that impairment of autophagy enhanced the anti-tumor effect of SDT through induction of apoptosis and necrosis, while caspase inhibition did not affect autophagic vacuoles formation or protect SDT induced cytotoxicity. The findings supported that autophagic vacuoles formed upstream and independently from caspase-dependent cell death. Additionally, the possible mechanism of SDT-induced autophagy was evaluated by measurement of ROS (reactive oxygen species) formation. Result suggested ROS play important role in initiating autophagy, possibly through the sono-damaged mitochondria being enclosed by autophagic vacuoles. All together, these data indicate that autophagy may be cytoprotective in our experimental system, and point to an important insight into how autophagy inhibitors, in combination with SDT may contribute a regimen for cancer therapy.
authors.affiliation: College of Life Sciences, Shaanxi Normal University, Shaanxi, Xi'an 710062, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wang
authors.forename: Pan
authors.initials: P
authors.lastname: Wang
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Su
authors.forename: Jie
authors.initials: J
authors.lastname: Hou
authors.forename: Quanhong
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000162:Acoustics; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D007939:Leukemia L1210; D051379:Mice; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011524:Protoporphyrins; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D011524:Protoporphyrins; D017382:Reactive Oxygen Species; C028025:protoporphyrin IX; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases