title: Cathepsin D inhibits oxidative stress-induced cell death via activation of autophagy in cancer cells.
abstract: Cathepsin D (CatD), a lysosomal aspartic protease, plays an essential role in tumor progression and apoptosis. However, the function of CatD in cell death is not yet fully understood. In this study, we identified CatD as one of up-regulated proteins in human malignant glioblastoma M059J cells that lack the catalytic subunit of DNA-PK compared with its isogenic M059K cells with normal DNA-PK activity. M059J cells were relatively more resistant to genotoxic stress than M059K cells. Overexpression of wild-type CatD but not catalytically inactive mutant CatD (D295N) inhibited H(2)O(2)-induced cell death in HeLa cells. Furthermore, knockdown of CatD expression abolished anti-apoptotic effect by CatD in the presence of H(2)O(2). Interestingly, high expression of CatD in HeLa cells significantly activated autophagy: increase of acidic autophagic vacuoles, LC3-II formation, and GFP-LC3 puncta. These results suggest that CatD can function as an anti-apoptotic mediator by inducing autophagy under cellular stress. In conclusion, inhibition of autophagy could be a novel strategy for the adjuvant chemotherapy of CatD-expressing cancers.
authors.affiliation: Clinical Research Institute, Gyeongsang National University Hospital, Jinju, Republic of Korea.
authors.forename: Young-Sool
authors.initials: YS
authors.lastname: Hah
authors.forename: Hae Sook
authors.initials: HS
authors.lastname: Noh
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Ha
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Ahn
authors.forename: Jong Ryeal
authors.initials: JR
authors.lastname: Hahm
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Cho
authors.forename: Deok Ryong
authors.initials: DR
authors.lastname: Kim
mesh_terms: D001343:Autophagy; D001483:Base Sequence; D001932:Brain Neoplasms / Q000473:pathology*; D002402:Cathepsin D / Q000502:physiology*; D016923:Cell Death / Q000502:physiology*; D045744:Cell Line, Tumor; D017931:DNA Primers; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D008854:Microscopy, Electron; D018384:Oxidative Stress / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D002402:Cathepsin D