Abstract
Very few growth inhibitors have been identified whichcan inhibit the proliferation of a broad spectrumof human breast cancer cell lines. CeReS-18, anovel cell surface sialoglycopeptide growth inhibitor, can reversiblyinhibit the proliferation of both estrogen receptor positive(MCF-7) and negative (BT-20) human breast cancer celllines. In addition, at concentrations above those requiredfor the reversible inhibition of cell proliferation, CeReS-18can also induce cell death in MCF-7 cells.Changes in nuclear and cytoplasmic morphology, characteristic ofapoptosis, were detected in MCF-7 cells treated witha cytotoxic concentration of CeReS-18, and internucleosomal DNAcleavage was also observed. The sensitivity of MCF-7and BT-20 cells to the biological properties ofCeReS-18 could be influenced by altering the calciumconcentration in the extracellular growth medium, such thatwhen the calcium concentration in the environment wasdecreased, an increased sensitivity to CeReS-18-induced growth inhibitionand cytotoxicity were observed. The addition of thecalcium chelating agent EGTA to MCF-7 cells, culturedin a normal calcium environment, could mimic theincreased sensitivity to the biological effects of CeReS-18observed under reduced calcium conditions.
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Cullen KJ, Yee D, Bates SE, Brunner N, Clarke R, Dickson RE, Huff KK, Paik S, Rosen N, Valverius E, Zugmaier G, Lippman ME: Regulation of human breast cancer by secreted growth factors. Acta Oncologica 28: 835–839, 1989
Osborne CK, Artega CL: Autocrine and paracrine growth regulation of breast cancer: Clinical implications. Breast Cancer Res and Treat 15: 3–11, 1990
McGuire WL: Hormone receptors: Their role in predicting prognosis and response to endocrine therapy. Semin Oncol 5: 428–433, 1978
Sharifi BG, Johnson TC, Khurana VK, Bascom CC, Fleenor TJ, Chu HH: Purification and characterization of a bovine cerebral cortex cell surface sialoglycopeptide that inhibits cell proliferation and metabolism. J Neurochem 46: 461–469, 1986
Johnson TC: Negative regulators of cell proliferation. Pharmac Ther 62: 247–265, 1994
Fattaey HK, Enebo DJ, Moos PM, Johnson TC: The identification of a naturally occurring cell surface growth inhibitor related to a previously described bovine sialoglycopeptide. J Cell Phys 52: 69–77, 1993
Sharifi BG, Johnson TC: Affinity labeling of the sialoglycopeptide antimitogen receptor. J Biol Chem 262(32): 15752–15755, 1987
Fattaey HK, Bascom CC, Johnson TC: Modulation of growth-related gene expression and cell cycle synchronization by a sialoglycopeptide inhibitor. Exp Cell Res 194: 62–68, 1991
Toole-Simms WE, Loder DK, Fattaey HK, Johnson TC: Effects of a sialoglycopeptide on early events associated with signal transduction. J Cell Phys 147: 292–297, 1991
Betz NA, Westhoff BA, Johnson TC: Role of calcium in growth inhibition induced by a novel cell surface sialoglycopeptide. J Cell Phys 164: 35–46, 1995
Wyllie AH, Kerr JFR, Currie AR: Cell death: The significance of apoptosis. Int Rev Cytol 68: 251–306, 1980
Kerr JFR, Harmon BV: Apoptosis: its significance in cancer and cancer therapy. Cancer 73(8): 2013–2026, 1994
Kerr JFR, Winterford CM, Harmon BV: Apoptosis — its significance in cancer and cancer therapy. Cancer 73(8): 2013–2026, 1994
Hennings H, Michael D, Cheng CK, Steinert PM, Holbrook KA, Yuspa SH: Calcium regulation of growth and differentiation of mouse epidermal cells in culture. Cell 19: 245–254, 1980
Bissonnette RP, Echeverri F, Mahboubi A, Green DR: Apoptotic cell death induced by c-myc is inhibited by bcl-2. Nature 359: 552–554, 1992
Betz NA, Fattaey HK, Johnson TC: Calcium influences sensitivity to growth inhibition induced by a novel cell surface sialoglycopeptide. J Cell Phys 161: 553–561, 1994
Fath I, Schweighoffer F, Rey I, Multon MC, Boiziau J, Duchesne M, Tocqui B: Cloning of a Grb2 isoform with apoptotic properties. Science 264: 971–974, 1994
Gazitt Y, Erdos GW: Fluctuations and ultrastructural localization of oncoproteins and cell cycle regulatory proteins during growth and apoptosis of synchronized AGF cells. Cancer Res 54: 950–956, 1994
Bardon S, Vignon F, Montcourrier P, Rochefort H: Steroid receptor-mediated cytotoxicity of an antiestrogen and an antiprogestin in breast cancer cells. Cancer Res 47: 1441–1448, 1987
Kyprianou N, English HF, Davidson NE, Isaacs JT: Programmed cell death during regression of the MCF-7 human breast cancer following estrogen ablation. Cancer Res 51: 162–166, 1991
Miller T, Beasang LA, Meneghini M, Lidgard G: Death-induced changes to the nuclear matrix: the use of anti-nuclear matrix antibodies to study agents of apoptosis. Biotechniques 15(6): 1042–1047, 1993
Oberhammer F, Wilson JW, Dive C, Morris ID, Hickman JA, Wakeling AE, Walker PR, Sikorska M: Apoptotic death in epithelial cells: cleavage of DNA to 300 and/or 50 kb fragments prior to or in the absence of internucleosomal fragmentation. EMBO J 12(9): 3679–3684, 1993
Kobayashi Y, Saheki T, Shinozawa T: Induction of PC12 cell death, apoptosis, by a sialoglycopeptide from bovine brain. Biochem Biophys Res Commun 203: 1554–1559, 1994
Gerschenson LE, Rotello RJ: Apoptosis: a different type of cell death. FASEB J 6: 2450–2455, 1992
Bertrand R, Sarang M, Jenkins J, Kerrigan D, Pommier Y: Differential induction of secondary DNA fragmentation by topoisomerase II inhibitors in human tumor cell lines with amplified c-myc expression. Cancer Res 51: 6280–6285, 1991
Bertrand R, Solary E, Jenkins J, Pommier Y: Apoptosis and its modulation in human promyelocytic HL-60 cells treated with DNA topoisomerase I and II inhibitors. Exp Cell Res 207: 388–397, 1993
McConkey DJ, Nicotera P, Hartzell P, Bellomo G, Wyllie AH, Orrenius S: Glucocorticoids activate a suicide process in thymocytes through an elevation of cytosolic Ca2+ concentration. Arch Biochem Biophys 269: 365–370, 1989
Matsubara K, Kubota M, Adachi S, Kuwakado K, Hirota H, Wakazona Y, Akiyama Y, Mikawa H: Different mode of cell death induced by calcium ionophore in human leukemia cell lines: Possible role of constitutive endonuclease. Exp Cell Res 210: 19–25, 1994
Rajotte D, Haddad P, Haman A, Cragoe Jr EJ, Hoang T: Role of protein kinase C and the Na+/H+ antiporter in suppression of apoptosis by granulocyte macrophage colony-stimulating factor and interleukin-3. J Biol Chem 267: 9980–9957, 1992
McConkey DJ, Hartzell P, Nicotera P, Orrenius S: Calciumactivated DNA fragmentation kills immature thymocytes. FASEB J 3: 1843–1849, 1989
Giannakis C, Forbes IJ, Zaleweski PD: Ca2+/Mg2+-dependent nuclease: Tissue distribution, relationship to inter-nucleosomal DNA fragmentation and inhibition by Zn2+. Biochem Biophys Res Commun 181: 915–920, 1991
Laster SM, Wood JG, Gooding LR: Tumor necrosis can induce both apoptotic and necrotic forms of cell lysis. J Immunol 141: 2629–2634, 1988
Woods KM, Fattaey H, Johnson TC, Chapes SK: Selective cytotoxicity of transformed cells but not normal cells by a sialoglycopeptide growth regulator in the presence of tumor necrosis factor. Biochem Biophys Res Commun 205: 215–220, 1994
Waring P: DNA fragmentation induced in macrophages by gliotoxin does not require protein synthesis and is preceded by raised inositol triphosphate levels. J Biol Chem 265: 14476–14480, 1990
Geier A, Haimshon M, Beery R, Hemi R, Lunenfeld B: Insulinlike growth factor-I inhibits cell death induced by cyclohexamide in MCF-7 cells: A model system for analyzing control of cell death. In Vitro Cell Dev Biol 28A: 725–729, 1992
Sarin A, Adams DH, Henkart PA: Protease inhibitors selectively block T cell receptor-triggered programmed cell death in a murine T cell hybridoma and activated peripheral T cells. J Exp Med 178: 1693–1700, 1993
Vaux DL: Toward an understanding of the molecular mechanisms of physiological cell death. Proc Natl Acad Sci USA 90: 786–789, 1993
Boise LH, Gonzalez-Garcia CE, Postema CE, Ding L, Lindstein T, Turka LA, Mao X, Nunez G, Thompson CB: bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 74: 597–608, 1993
Hengartner M, Horvitz HR: C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2. Cell 76: 665–676, 1994
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Betz, N.A., Fattaey, H.K., Westhoff, B.A. et al. CeReS-18, a novel cell surface sialoglycopeptide, induces cell cycle arrest and apoptosis in a calcium-sensitive manner. Breast Cancer Res Treat 42, 137–148 (1997). https://doi.org/10.1023/A:1005735723808
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DOI: https://doi.org/10.1023/A:1005735723808