title: Resistance of rho(0) cells against apoptosis.
abstract: Mitochondrion is one of the master players in both apoptosis and necrosis. However, most previous articles report that mitochondrial DNA-depleted cells without oxidative phosphorylation underwent apoptosis by several apoptotic effectors as efficiently as their parental cells, suggesting that intact mitochondrial function is dispensable for the progression of apoptosis. We studied the role of mitochondrial function in several apoptosis models. TRAIL, a recently identified member of the TNF family with cytotoxicity on a wide variety of transformed cells, killed SK-Hep1 cells with characteristic features of apoptosis such as DNA fragmentation, sub-G1 ploidy peak, and cytochrome c translocation. In contrast with parental cells, mitochondrial DNA-deficient SK-Hep1 rho(0) cells were resistant to TRAIL-induced apoptosis. Dissipation of mitochondrial potential or cytochrome c translocation did not occur in rho(0) cells after TRAIL treatment. Bax translocation also was absent in rho(0) cells, accounting for the failure of cytochrome c release in rho(0) cells. SK-Hep1 rho(0) cells were resistant to other death effectors such as staurosporine. Our results indicate that apoptosis of SK-Hep1 hepatoma cells is dependent on intact mitochondrial function. Because aged cells or tumor cells have frequent mutations or deletions of mitochondrial DNA, they might acquire the ability to evade apoptosis or tumor surveillance imposed by TRAIL or other death effectors in vivo, accounting for the selection advantage of cancer cells and frequent development of cancer in aged individuals.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Kangnam-ku, Seoul 135-710, Korea. mslee@smc.samsung.co.kr
authors.forename: Myung-Shik
authors.initials: MS
authors.lastname: Lee
authors.forename: Ja-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Park
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D045744:Cell Line, Tumor; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D019311:Staurosporine / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; D004272:DNA, Mitochondrial; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D019311:Staurosporine