[en] Ascorbate and menadione (Apatone) in a ratio of 100:1 kills tumor cells by autoschizis. In this study, vitamin-induced changes in nucleolar structure were evaluated as markers of autoschizis. Human bladder carcinoma (T24) cells were overlain with vitamins or with culture medium. Supernatants were removed at 1-hr intervals from 1 to 4 hr, and the cells were washed with PBS and prepared for assay. Apatone produced marked alterations in nucleolar structure including redistribution of nucleolar components, formation of ring-shaped nucleoli, condensation and increase of the proportion of perinucleolar chromatin, and the enlargement of nucleolar fibrillar centers. Immunogold labeling of the nucleolar rRNA revealed a granular localization in treated and sham-treated cells, and immunogold labeling of the rDNA revealed a shift from the fibrillar centers to the condensed perinucleolar chromatin. Fibrillarin staining shifted from the fibrillar centers and adjacent regions to a more homogeneous staining of the entire nucleolus and was consistent with the percentage of autoschizic cells detected by flow cytometry. Because autoschizis entails sequential reactivation of DNase I and DNase II, and because the fibrillarin redistribution following DNase I and Apatone treatment is identical, it appears that the nucleolar and fibrillarin changes are markers of autoschizis.
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Bibliography
Bellamy OC, Malcomson DG, Harrison DJ, Wyllie AH (1995) Cell death in health and disease: the biology and regulation of apoptosis. Semin Cancer Biol 6:3-16
Bernhard W (1966) Ultrastructural aspects of the normal and pathological nucleolus in mammalian cells. Natl Cancer Inst Monogr 23:13-38
Bernhard W (1971) Drug-induced changes in the interphase nucleus. Adv Cytopharmacol 1:49-67
Biggiogera M, Trenatani A, Martin TE, Pellicciari C (1999) Terminal differentiation of erythroblasts leads toRNP segregation and formation of heterogeneous ectopic RNP-derived structures. Histochem Cell Biol 112:473-477
Bortul R, Zweyer M, Billi AM, Tabellini G, Ochs RL, Bareggi R, Cocco L, et al. (2001) Nuclear changes in necrotic HL-60 cells. J Cell Biochem Suppl 36:19-31
Busch H, Smetana K (1970) The Nucleolus. New York, Academic Press, 472-510
Chan PK (1992) Characterization and cellular localization of nucleophosmin/B23 in HeLa cells treated with cytotoxic agents (Studies of B23-translocation mechanism). Exp Cell Res 203:174-181
Chan PK, Aldrich MB, Chakrabarty S (1988) Assessment of tumor cell sensitivity to mitomycin C by "B23 translocation" assay. J Biol Chem 263:10608-10612
Chan PK, Qi Y, Amley J, Koller CA (1996) Quantitation of the nucleophosmin/B23 translocation using imaging analysis. Cancer Lett 100:191-197
Dynlacht JR, Earles M, Henthorn J, Roberts ZV, Howard EW, Seno JD, Sparling D, et al. (1999) Degradation of the nuclear matrix is a common element during radiation-induced apoptosis and necrosis. Radiat Res 152:590-603
Ervin E, Jamison JM, Gilloteaux J, Docherty JJ, Summers JL (1998) Characterization of the early events in vitamin C and K3-induced death of human bladder tumor cells. Scanning 20:210-211
Fakan S, Puvion E (1980) The ultrastructural visualization of nucleolar and extranucleolar RNA synthesis and distribution. Int Rev Cytol 65:255-299
Falcieri E, Gobbi P, Zamai L, Vitale M (1994) Ultrastructural features of apoptosis. Scanning Microsc 8:653-666
Farber E, Roberts J (1971) Response of cells to inhibition of synthesis of DNA, RNA and protein. Biochem Pharmacol 20:1023-1026
Finch RA, Chang DC, Chan PK (1995) GTP gamma S restores nucleophosmin (NPM) localization to nucleoli of GTP-depleted HeLa cells. Mol Cell Biochem 146:171-178
Freeman JW, Busch RK, Gyorkey F, Gyorkey P, Ross BE, Busch H (1988) Identification and characterization of a human proliferation-associated nucleolar antigen with a molecular weight of 120,000 expressed in early G1 phase. Cancer Res 48:1244-1251 (Pubitemid 18075541)
Gilloteaux J, Jamison JM, Arnold D, Ervin E, Eckroat L, Docherty JJ, Neal D, et al. (1998a) Cancer cell necrosis by autoschizis: synergism of antitumor activity of vitamin C:vitamin K3 on human bladder carcinoma T24 cells. Scanning 20:564-575
Gilloteaux J, Jamison JM, Arnold D, Jarjoura D, Von Greuningen V, Summers JL (2003a) Autoschizis of human ovarian carcinoma cells: scanning electron and light microscopy of a new cell death induced by sodium ascorbate:menadione treatment. Scanning 25:137-149 (Pubitemid 36818813)
Gilloteaux J, Jamison JM, Arnold D, Neal D, Summers JL (2006) Morphology and DNA degeneration during autoschizic cell death in bladder carcinoma T24 cells induced by ascorbate and menadione treatment. Anat Rec A Discov Mol Cell Evol Biol 288:58-83
Gilloteaux J, Jamison JM, Arnold D, Summers JL (2001a) Autoschizis: another cell death for cancer cells induced by oxidative stress. Ital J Anat Embryol 106(suppl 1):79-92
Gilloteaux J, Jamison JM, Arnold D, Taper HS, Summers JL (1999a) A new cell death, autoschizis facilitated by oxidative stress induced by vitamins C:K3 in bladder and prostate cancer. Mol Biol Cell 10:44A
Gilloteaux J, Jamison JM, Arnold D, Taper HS, Summers JL (2001b) Ultrastructural aspects of autoschizis: a new cancer cell death induced by the synergistic action of ascorbate/menadione on human bladder carcinoma cells. Ultrastruct Pathol 25:183-192 (Pubitemid 32607291)
Gilloteaux J, Jamison JM, Arnold D, Taper HS, von Greunigen VE, Summers JL (2003b) Microscopic aspects of autoschizic cell death in human ovarian carcinoma (2774) cells following vitamin C, vitamin K3 or vitaminC:K3 treatment. Microsc Microanal 9:311-329
Gilloteaux J, Jamison JM, Ervin E, Taper HS, Summers JL (1998b) SEM and TEM aspects of the synergistic antitumor activity of vitamin C/vitamin K 3 combinations against human T24 bladder carcinoma: another kind of cell death? Scanning 20:208-210
Gilloteaux J, Jamison JM, Lorimer HE, Jarjoura D, Taper HS, Calderon PB, Neal DR, et al. (2004) Autoschizis: a new form of cell death for human ovarian carcinoma cells following ascorbate: menadione treatment. Nuclear and DNA degradation. Tissue Cell 36:197-209
Gilloteaux J, Jamison JM, Neal DR, Loukas M, Doberzstyn T, Summers JL (2010) Cell damage and death by autoschizis in human bladder (RT4) carcinoma cells resulting from treatment by ascorbate and menadione. Ultrastruct Pathol 34:140-160
Gilloteaux J, Jamison JM, Neal DR, Summers JL (2005) Cell death by autoschizis in TRAMP prostate carcinoma cells as a result of treatment by ascorbate:menadione combination. Ultrastruct Pathol 23:221-235 (Pubitemid 40993748)
Gilloteaux J, Jamison JM, Summers JL (2001c) Cell death by autoschizis in human carcinoma cell lines: nucleus, DNA detection and degradation. Mol Cell Biol 12:497A
Gilloteaux J, Jamison JM, Vijayalaksmi M, Giammar D, Summers JL (1995) SEM and TEM aspects of synergistic antitumor activity of vitamin C-vitamin K3 combinations against human prostatic carcinoma cells. Scanning Microsc 9:159-173
Gilloteaux J, Jamison JM, von Greunigen VE, Arnold D, Summers JL (1999b) Autoschizis in ovarian carcinoma cells MDAH as a result of treatment by combined vitamin C and K3 treatment. Scanning 22:119-120
Hadjiolov AA (1985) Ribosome biogenesis in the life cycle of normal and cancer cells. In Alfert M, Beerman W, Goldstein L, Porter KR, Sitte P, eds. The Nucleolus and Ribosome Biogenesis, Cell Biology Monographs, vol 12. Wien, Springer-Verlag, 165-196
Jamison JM, Gilloteaux J, Nassiri MR, Venugopal M, Neal DR, Summers JL (2004) Cell cycle arrest and autoschizis in a human bladder carcinoma cell line following vitamin C and vitamin K3 treatment. Biochem Pharmacol 67:337-351
Jamison JM, Gilloteaux J, Taper HS, Buc Calderon P, Perlaky L, Thiry M, Neal DR, et al. (2005) The in vitro and in vivo antitumor activity of vitamin C:K3 combinations against prostate cancer. In Lucas JL, ed. Trends in Prostate Cancer Research, vol. 7. Hauppauge, NY, Nova Science Publisher, 189-236
Jamison JM, Gilloteaux J, Taper HS, Summers JL (2001) Evaluation of the in vitro and in vivo antitumor activities of vitamin C and K3 combinations against human prostate cancer. J Nutr 131:158S-160S
Jamison JM, Gilloteaux J, Thiry M, Authelet M, Goessens G, Summers JL (1998) Ultrastructural nucleolar alterations induced by an ametantrone-poly r(A-U) complex. Tissue Cell 30:475-484
Jamison JM, Gilloteaux J, Venugopal M, Koch JA, Nicastro E, Docherty JJ, Jasso J, et al. (1997) Vitamin C and K3-induced oxidative stress in human prostate tumor cells: mitochondrial ultrastructural alterations. Microsc Microanal 3:23-24
Jamison JM, Gilloteaux J, Venugopal M, Koch JA, Sowick C, Shah R, Summers JL (1996) Flow cytometric and ultrastructural aspects of the synergistic antitumor activity of vitamin C-vitamin K3 combinations against human prostate carcinoma cells. Tissue Cell 28:687-701
Kerr JFR (1971) Shrinkage necrosis: a distinct mode of cellular death. J Pathol 105:13-20
Kerr JFR,Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetics. Br J Cancer 26:239-257
Majno G, Joris I (1995) Apoptosis, oncosis and necrosis: an overview of cell death. Am J Pathol 146:3-15
Martelli AM, Robuffo I, Bortul R, Ochs RL, Luchetti F, Cocco L, Zweyer M, et al. (2000) Behavior of nucleolar proteins during the course of apoptosis in camptothecin-treated HL-60 cells. J Cell Biochem 78:264-277 (Pubitemid 30415903)
Martelli AM, Zweyer M, Ochs RL, Tazzari PL, Tabellini G, Narducci P, Bortul R (2001) Nuclear apoptotic changes: an overview. J Cell Biochem 82:634-646
Ochs R, Lischwe M, O'Leary P, Busch H (1983) Localization of nucleolar phosphoproteins B23 and C23 during mitosis. Exp Cell Res 146:139-149
Ochs RL, Lischwe MA, Spohn WH, Busch H (1985) Fibrillarin: a new protein of the nucleolus identified by autoimmune serum. Biol Cell 54:123-134
Reimer G, Pollard KM, Penning CA, Ochs RL, Lischwe MA, Busch H, Tan EM (1987) Monoclonal autoantibody from a (New Zealand black x New Zealand white) F-1 mouse and some human scleroderma sera target an Mr 34,000 nucleolar protein of the U3 RNP particle. Arthitis Rheum 30:793-800 (Pubitemid 17145216)
Shah GM, Shah RG, Poirier GG (1996) Different cleavage patterns for poly(ADP-ribose) polymerase during necrosis and apoptosis in HL-60 cells. Biochem Biophys Res Commun 229:838-844
Simard R, Langelier Y, Rosemonde M, Maestracci N, Royal A (1974) Inhibitors as tools in the structure and function of the nucleus. In Busch H, ed. The Cell Nucleus, vol 3. New York, Academic Press, 447-487
Simard S, Bernhard W (1966) Le phénomène de la ségrégation nucléolaire: spécificité d'action de certains antimétabolites. Int J Cancer 1:463-479
Schwarzacher HG, Wachtler F (1993) The nucleolus. Anat Embryol (Berl) 188:515-536
Stuppia L, Gobbi P, Zamai L, Palka G, Vitale M, Falcieri E (1996) Morphometric and functional study of apoptotic cell chromatin. Cell Death Differ 3:397-405
Taper HS (2008) Altered deoxyribonuclease activity in cancer cells and its role in non toxic adjuvant cancer therapy with mixed vitamins C and K3. Anticancer Res 28:2727-2732
Taper HS, Jamison JM, Gilloteaux J, Gwin CA, Gordon T, Summers JL (2001) In vivo reactivation of DNases in implanted human prostate tumors after administration of a vitamin C/K3 combination. J Histochem Cytochem 49:109-119
Thiry M (1992a) Highly sensitive immunodetection of DNA on sections with exogenous terminal deoxynucleotidyl transferase and nonisotopic nucleotide analogs. J Histochem Cytochem 40:411-419
Thiry M (1992b) New data concerning the functional organization of the mammalian cell nucleolus: detection of RNA and rRNA by in situ molecular immunocytochemistry. Nucleic Acids Res 20:6195-6200
Thiry M (1995) Nucleic acid compartmentalization within the cell nucleus by in situ transferase-immunogold techniques. Microsc Res Tech 31:4-21
Thiry M, Jamison JM, Gilloteaux J, Summers JL, Goessens G (1997) Ultrastructural nucleolar alterations induced by an ametantrone/ polyr(A-U) complex. Exp Cell Res 236:275-284
Valdez BC, Henning D, Busch RK, Woods K, Flores-Rozas H, Hurwitz J, Perlaky L, et al. (1996) A nucleolar RNA helicase recognized by autoimmune antibodies from a patient with watermelon stomach disease. Nucleic Acids Res 24:1220-1224 (Pubitemid 26102669)
Venugopal M, Jamison JM, Gilloteaux J, Koch JA, Summers M, Giammar DM, Sowick C, et al. (1996a) Synergistic antitumoractivity of vitamin C and K 3 on human urologic tumor cell lines. Life Sci 59:1389-1400
Venugopal M, Jamison JM, Gilloteaux J, Koch JA, Summers M, Hoke J, Sowick C, et al. (1996b) Synergistic antitumor activity of vitamins C and K 3 against human prostate carcinoma cell lines. Cell Biol Int 20:787-797
Verrax J, Cadrobbi J, Delvaux M, Jamison JM, Gilloteaux J, Summers JL, Taper HS, et al. (2003) The association of vitamins C and K3 kills cancer cells mainly by autoschizis, a novel form of cell death. Basis for their potential use as coadjuvants in anticancer therapy. Eur J Med Chem 38:451-457
Verrax J, Cadrobbi J, Marques C, Taper HS, Habraken Y, Piette J, Calderon PB (2004) Ascorbate potentiates the cytotoxicity of menadione leading to an oxidative stress that kills cancer cells by a non-apoptotic caspase-3 independent form of cell death. Apoptosis 9:223-233 (Pubitemid 38987599)
Verrax J, Stockis J, Tison A, Taper HS, Calderon PB (2006) Oxidative stress by ascorbate/menadione association kills K562 human chronic myelogenous leukaemia cells and inhibits its tumour growth in nude mice. Biochem Pharmacol 72:671-680 (Pubitemid 44233542)
von Gruenigen VE, Jamison JM, Gilloteaux J, Lorimer HE, Summers M, Pollard RR, Gwin CA, et al. (2003) The in vitro antitumor activity of vitamins C and K3 against ovarian carcinoma. Anticancer Res 23:3279-3287
Wu MH, Lam CY, Yung BY (1995) Translocation of nucleophosmin from nucleoli to nucleoplasm requires ATP. Biochem J 305:987-992
Wyllie AH, Kerr JF, Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68:251-306
Wyllie AH, Morris RG, Smith AL, Dunlop D (1984) Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol 142:67-77
Yung BY, Bor AM, Chan PK (1990) Short exposure to actinomycin D induces "reversible" translocation of protein B23 as well as "reversible" inhibition of cell growth and RNA synthesis in HeLa cells. Cancer Res 50:5987-5991
Yung BY, Busch H, Chan PK (1985) Translocation of nucleolar phosphoprotein B23 (37 kDa/pI 5.1) induced by selective inhibitors of ribosome synthesis. Biochim Biophys Acta 826:167-173
Zhang W, Negoro T, Satoh K, Jiang Y, Hashimoto K, Kikuchi H, Nishikawa H, et al. (2001) Synergistic cytotoxic action of vitamin C and vitamin K 3. Anticancer Res 21:3439-3444
Zweyer M, Bareggi R, Grill V, Soranzo MR, Marugg RA, Riederer BM, Narducci P, et al. (1995) Behaviour of nuclear matrix proteins during camptothecin-induced apoptosis in HL-60 human leukemia cells. Exp Cell Res 221:27-40
Zweyer M, Riederer BM, Ochs RL, Fackelmayer FO, Kohwi-Shigematsu T, Bareggi R, Narducci P, et al. (1997) Association of nuclear matrix proteins with fibrogranular nuclear bodies in cell lines undergoing apoptosis. Exp Cell Res 230:325-336
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