title: Pseudolaric acid B-induced autophagy contributes to senescence via enhancement of ROS generation and mitochondrial dysfunction in murine fibrosarcoma L929 cells.
abstract: Pseudolaric acid B (PAB) is the primary biologically active compound isolated from the root bark of P. kaempferi Gordon. Our previous study demonstrated that PAB induced mitotic catastrophe in L929 cells and indicated that only a small percentage (12%) of the cells undergoing mitotic catastrophe displayed an apoptotic phenotype after PAB treatment for 72 h. In this study, we found that a minority of the cells undergoing mitotic catastrophe ended in apoptosis, and a majority of them entered a period of senescence. Further data confirmed that PAB induced autophagy, reactive oxygen species (ROS) generation, and mitochondrial dysfunction in L929 cells. Subsequently, we found that autophagy inhibitors significantly delayed the senescence process, indicating that autophagy facilitated senescence. Moreover, ROS scavenger significantly decreased the autophagic level and improved mitochondrial function. Additionally, autophagy inhibitors effectively reduced ROS levels and ameliorated mitochondrial function. In conclusion, autophagy promoted senescence via enhancement of ROS generation and mitochondrial dysfunction in PAB-treated L929 cells.
authors: China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, China.
authors: Min
authors: M
authors: Qi
authors: Simiao
authors: S
authors: Fan
authors: Guodong
authors: G
authors: Yao
authors: Zhao
authors: Z
authors: Li
authors: Haiyan
authors: H
authors: Zhou
authors: Shin-ichi
authors: S
authors: Tashiro
authors: Satoshi
authors: S
authors: Onodera
authors: Mingyu
authors: M
authors: Xia
authors: Takashi
authors: T
authors: Ikejima
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology*; D016922:Cellular Senescence; D004224:Diterpenes / Q000494:pharmacology*; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D016166:Free Radical Scavengers / Q000494:pharmacology; D051379:Mice; D008928:Mitochondria / Q000473:pathology*; D008938:Mitosis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D004224:Diterpenes; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; C058391:pseudolaric acid B