title: Increased P-glycoprotein expression in mitochondria is related to acquired             multidrug resistance in human hepatoma cells depleted of mitochondrial DNA.
abstract: Mitochondrial DNA-depleted ρ0 cells are resistant to apoptosis, but the             mechanism remains unclear. A human hepatoma cell line (SK-Hep1) depleted of mtDNA             (ρ0SK-Hep1) was induced by ethidium bromide treatment. The ρ0SK-Hep1 cells were             resistant to both doxorubicin- and cisplatin-induced apoptosis, while cybrids             (SK-Hep1Cyb) prepared by fusing ρ0SK-Hep1 cells with platelets showed restored             susceptibility to both drugs. We observed P-glycoprotein and MRP1 were both overexpressed             in ρ0 cells, and more P-glycoproteins were localized in the mitochondria and were             functionally active. ρ0 cells showed resistance to chemotherapeutic drug-induced             apoptosis. The increased expression and localization of P-glycoproteins in the             mitochondria of ρ0 cells may facilitate the exclusion of chemotherapeutic drugs             from the mitochondria to the cytosol.
authors: Department of Gastroenterology, Xinqiao Hospital, Third Military                     Medical University, Chongqing 400037, P.R. China.
authors: Xianlong
authors: X
authors: Ling
authors: Yuqi
authors: Y
authors: He
authors: Guoqiao
authors: G
authors: Zhang
authors: Yuan
authors: Y
authors: Zhou
authors: Bin
authors: B
authors: Yan
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial; D008856:Microscopy, Fluorescence; D008930:Mitochondria, Liver / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004272:DNA, Mitochondrial; D004317:Doxorubicin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C421109:multidrug resistance-associated protein 1