title: Hypoxia-mediated autophagic flux inhibits silver nanoparticle-triggered apoptosis in human lung cancer cells.
abstract: Solid tumors are frequently associated with resistance to chemotherapy because the fraction of hypoxic tumor cells is substantial. To understand the underlying mechanism of hypoxia on silver nanoparticle (AgNPs)-induced apoptosis, the expression of hypoxia-inducible factor (HIF)-1α, a hallmark of hypoxia, was measured in the presence and absence of AgNPs. The results showed that HIF-1α expression was upregulated after AgNPs treatment under both hypoxic and normoxic conditions. Cell viability assays showed that AgNPs promoted cell death in cancer cells but not in non-cancer cells, as cancer cells are slightly more acidic than normal cells. However, reactive oxygen species generation induced by AgNPs in lung cancer cells caused high susceptibility to oxidative stress, whereas pre-exposure to hypoxia blocked AgNPs-induced oxidative stress. Notably, HIF-1α inhibited AgNPs-induced mitochondria-mediated apoptosis by regulating autophagic flux through the regulation of ATG5, LC3-II, and p62. Further, cell viability after treatment of cancer cells with AgNPs under hypoxic conditions was lower in HIF-1α siRNA-transfected cells than in control siRNA-transfected cells, indicating that HIF-1α knockdown enhances hypoxia induced decrease in cell viability. Our results suggest that hypoxia-mediated autophagy may be a mechanism for the resistance of AgNPs-induced apoptosis and that strategies targeting HIF-1α may be used for cancer therapy.
authors: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Jae-Kyo
authors: JK
authors: Jeong
authors: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Sangiliyandi
authors: S
authors: Gurunathan
authors: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Min-Hee
authors: MH
authors: Kang
authors: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Jae Woong
authors: JW
authors: Han
authors: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Joydeep
authors: J
authors: Das
authors: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Yun-Jung
authors: YJ
authors: Choi
authors: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Deug-Nam
authors: DN
authors: Kwon
authors: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Ssang-Goo
authors: SG
authors: Cho
authors: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Chankyu
authors: C
authors: Park
authors: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Han Geuk
authors: HG
authors: Seo
authors: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Hyuk
authors: H
authors: Song
authors: Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Jin-Hoi
authors: JH
authors: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis; D001343:Autophagy; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004351:Drug Resistance; D020869:Gene Expression Profiling; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D008175:Lung Neoplasms / Q000503:physiopathology*; D053758:Nanoparticles / Q000633:toxicity*; D012834:Silver / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012834:Silver