title: Peneciraistin C induces caspase-independent autophagic cell death through mitochondrial-derived reactive oxygen species production in lung cancer cells.
abstract: Peneciraistin C (Pe-C) is a novel spiroketal compound isolated from the saline soil derived fungus Penicillium raistrickii. Our previous study showed that Pe-C exerted a potent cytotoxic effect on many kinds of cancer cell lines, especially on human lung cancer A549 cells. Here, we report the anticancer mechanisms of Pe-C in a variety of lung cancer cells. The results showed that Pe-C induced caspase-independent autophagic cell death and elevated mitochondrial-derived reactive oxygen species levels. Interestingly, if autophagy was blocked by 3-methyladenine or Atg5 siRNA, Pe-C triggered a shift from autophagic cell death into caspase-dependent apoptotic cell death. In addition, cotreatment with the antioxidant N-acetyl-(L)-cysteine or Mito-TEMPO could effectively reverse the effect of the enhanced reactive oxygen species production, which in turn almost completely prevented the cell death induced by Pe-C. Thus, this study provided new insights into the mechanisms underlying Pe-C-mediated cell death, which indicated that Pe-C could be a potential drug candidate for therapy of lung cancers.
authors: Department of Pharmaceutical Sciences, Binzhou Medical University, Yantai, China.
authors: Xiaohong
authors: X
authors: Pan
authors: Desheng
authors: D
authors: Liu
authors: Juan
authors: J
authors: Wang
authors: Xiuli
authors: X
authors: Zhang
authors: Miaomiao
authors: M
authors: Yan
authors: Dehai
authors: D
authors: Zhang
authors: Jinjin
authors: J
authors: Zhang
authors: Weizhong
authors: W
authors: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001343:Autophagy / Q000187:drug effects*; D000071187:Autophagy-Related Protein 5; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013141:Spiro Compounds / Q000494:pharmacology*
chemical_list: C502778:ATG5 protein, human; D000970:Antineoplastic Agents; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D017382:Reactive Oxygen Species; D013141:Spiro Compounds; C587960:peneciraistin C; D020169:Caspases
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