Drugs

, Volume 54, Issue 4, pp 511–532 | Cite as

Apoptosis

Clinical Relevance and Pharmacological Manipulation
Review Article

Summary

Apoptosis, often synonymously used with the term ‘programmed cell death’, is an active, genetically controlled process that removes unwanted or damaged cells.

Suppression, overexpression or mutation of a number of genes which orchestrate the apoptotic process are associated with disease. The diseases in which apoptosis has been implicated can be grouped into 2 broad groups: those in which there is increased cell survival (i.e. associated with inhibition of apoptosis) and those in which there is excess cell death (where apoptosis is overactive).

Diseases in which there is an excessive accumulation of cells include cancer, autoimmune disorders and viral infections. Deprivation of trophic factors is known to induce apoptosis in cells dependent on them for survival. This fact has been exploited in the use of antiandrogens or antiestrogens in the management of prostate or breast cancer.

Haemopoietic growth factors like granulocyte-macrophage colony stimulating factor (GM-CSF) or interleukin-3 prevent apoptosis in target cells and modulation of levels of these factors has been tried in the prevention of chemotherapy-induced myelosuppression. Until recently, it was thought that cytotoxic drugs killed target cells directly by interfering with some life-maintaining function. However, of late, it has been shown that exposure to several cytotoxic drugs with disparate mechanisms of action induces apoptosis in both malignant and normal cells.

Physiological regulation of cell death is essential for the removal of potentially autoreactive lymphocytes during development and the removal of excess cells after the completion of an immune response. Recent work has clearly demonstrated that dysregulation of apoptosis may underlie the pathogenesis of autoimmune diseases by allowing abnormal autoreactive lymphocytes to survive.

AIDS and neurodegenerative disorders like Alzheimer’s or Parkinson’s disease represent the most widely studied group of disorders where an excess of apoptosis has been implicated. Amyotrophic lateral sclerosis, retinitis pigmentosa, epilepsy and alcoholic brain damage are other neurological disorders in which apoptosis has been implicated.

Apoptosis has been reported to occur in conditions characterised by ischaemia, e.g. myocardial infarction and stroke. The liver is a site where apoptosis occurs normally. This process has also been implicated in a number of liver disorders including obstructive jaundice. Hepatic damage due to toxins and drugs is also associated with apoptosis in hepatocytes. Apoptosis has also been identified as a key phenomenon in some diseases of the kidney, i.e. polycystic kidney, as well as in disorders of the pancreas like alcohol-induced pancreatitis and diabetes.

Keywords

Tamoxifen Amyotrophic Lateral Sclerosis Berberine Spinal Muscular Atrophy Retinitis Pigmentosa 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetics. Br J Cancer 1972; 26: 239–57PubMedGoogle Scholar
  2. 2.
    Herman Steller. Mechanisms and genes of cellular suicide. Science 1995; 267: 1445–9Google Scholar
  3. 3.
    Cohen JJ. Apoptosis. Immunol Today 1993; 14(3): 126–30PubMedGoogle Scholar
  4. 4.
    Kerr JFR, Harmon BV. Definition and incidence of apoptosis: an historical perspective. In: Tomie LD, Cope FO, editors. Apoptosis: the molecular basis of cell death. Cold Spring Harbor: Laboratory Press, 1991: 5–29Google Scholar
  5. 5.
    Carson DA, Rebeiro JM. Apoptosis and disease. Lancet 1993; 341: 1251–4PubMedGoogle Scholar
  6. 6.
    Singh N. Apoptosis — new concepts in molecular medicine. Ind J Clin Biochem 1995; 10(2): 54–6Google Scholar
  7. 7.
    Kontogeorgos G, Kovacs K. Apoptosis in endocrine glands. Endocrine Pathology 1995; 6: 257–65PubMedGoogle Scholar
  8. 8.
    Schwartzman RA, Cedlowski JA. Apoptosis: the biochemistry and molecular biology of programmed cell death. Endocr Rev 1993; 14(2): 133–51PubMedGoogle Scholar
  9. 9.
    Arends MJ, Wyllie AH. Mechanisms and roles in pathology. Int Rev Exp Pathol 1991; 32: 223–54PubMedGoogle Scholar
  10. 10.
    Arends MJ, Morris RG, Wyllie AH. Apoptosis: the role of the endonuclease. Am J Pathol 1990; 36: 593–608Google Scholar
  11. 11.
    Wyllie AH. Glucocorticoid induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 1980; 284: 555–6PubMedGoogle Scholar
  12. 12.
    Bortner CD, Oldenburg NBS, Cedlowski JA. The role of DNA fragmentation in apoptosis. Trends Cell Biol 5: 21–6Google Scholar
  13. 13.
    Knight CR, Rees RC, Griffin M. Apoptosis: a potential role for cytosolic transglutaminase and its importance in tumour progression. Biochem Biophys Acta 1991; 1096: 312–8PubMedGoogle Scholar
  14. 14.
    Gavrieli Y, Sherman Y, Bensasson SA. Identification of programmed cell death in situ via special labelling of nuclear DNA fragments. J Cell Biol 1992; 119: 493–501PubMedGoogle Scholar
  15. 15.
    Kokawa K, Toshihiko S, Ryosuke N. Apoptosis in the human uterine endometrium during the menstrual cycle. J Clin Endocrinol Metab 1996; 81(11): 4144–7PubMedGoogle Scholar
  16. 16.
    Hamel W, Dazin P, Israel M. Adaptation of a simple flow cytometric assay to identify different stages during apoptosis. Cytometry 1996; 25: 173–81PubMedGoogle Scholar
  17. 17.
    Dive C, Gregory CD, Phipps DJ, et al. Analysis and discrimination of necrosis and apoptosis (programmed cell death) by multiparameter flow cytometry. Biochem Biophys Acta 1992; 1133: 275–85PubMedGoogle Scholar
  18. 18.
    Gong J, Traganos F, Darsynkiewicz Z. A selective procedure for DNA extracting from apoptotic cells applicable for gel electrophoresis and flow cytometry. Anal Biochem 1994; 218: 314–9PubMedGoogle Scholar
  19. 19.
    McConkey DJ, Hartzeil P, Duddy SK, et al. 2,3,7,8-tetrachlorobenzo-p-dioxin kills immature thymocytes by calcium mediated endonuclease activation. Science 1988; 242: 256–9PubMedGoogle Scholar
  20. 20.
    Gregory CD, Dive C, Henderson S, et al. Activation of Epstein-Barr virus latent genes protects human B cells from death by apoptosis. Nature 1991; 349: 612–4PubMedGoogle Scholar
  21. 21.
    Majno G, Joris I. Apoptosis, oncosis and necrosis: an overview of cell death. Am J Pathol 1995; 146(1): 3–15PubMedGoogle Scholar
  22. 22.
    Lowe S, Bodis S, McClatchey A, et al. p53 status and efficacy of cancer treatment in vivo. Science 1994; 266: 807–10PubMedGoogle Scholar
  23. 23.
    Appleby DW, Modak SP. DNA degradation in terminally differentiating lens fibre from chick embryos. Proc Natl Acad Sci USA 1977; 74: 5579–83PubMedGoogle Scholar
  24. 24.
    Darzynkiewicz Z, Bruno S, Del Bino G, et al. Features of apoptotic cells measured by flow cytometry. Cytometry 1992; 13: 795–808PubMedGoogle Scholar
  25. 25.
    Telford WG, King LE, Fraker PJ. Rapid quantitation of apoptosis in pure and heterogeneous cell populations using flow cytometry. J Immunol Method 1994; 172: 1–16, 25Google Scholar
  26. 26.
    Frankfurt OS. Detection of apoptosis in leukemic and breast cancer cells with monoclonal antibody to single stranded DNA. Anticancer Res 1994; 14(5A): 1861–9PubMedGoogle Scholar
  27. 27.
    Ellis PA, Smith IE, McCarthy K, et al. Preoperative chemotherapy induces apoptosis in early breast cancer [letter]. Lancet 1997; 349: 849PubMedGoogle Scholar
  28. 28.
    Moreira LF, Naomoto Y, Hamada M, et al. Assessment of apoptosis in esophageal carcinoma preoperative treatment by chemotherapy and radiology. Anticancer Res 1995; 15(2): 639–44PubMedGoogle Scholar
  29. 29.
    Chen DF, Schneider GE, Martinou J-C, et al. Bcl-2 promotes regeneration of severed axons in mammalian CNS. Nature 1997; 385: 434–9PubMedGoogle Scholar
  30. 30.
    Vaux DL, Strasser A. The molecular biology of apoptosis. Proc Natl Acad Sci USA 1996; 93: 2239–44PubMedGoogle Scholar
  31. 31.
    White E. Life, death and the pursuit of apoptosis. Genes Dev 1996; 10: 1–15PubMedGoogle Scholar
  32. 32.
    Linn SC, Honkoop AH, Hockman K, et al. p53 and P-glycoprotein are often co-expressed and are associated with poor prognosis. Br J Cancer 1996; 74: 63–8PubMedGoogle Scholar
  33. 33.
    Aas T, Borresen AL, Geisler S, et al. Specific p53 imitations are associated with de novo resistance to doxorubicin in breast cancer patients. Nat Med 1996; 2(7): 811–4PubMedGoogle Scholar
  34. 34.
    Hockenbery DM, Zutler M, Hickey W, et al. Bcl-2 protein is topographically restricted in tissues characterised by apoptotic death. Proc Natl Acad Sci USA 1991; 88: 6961–5PubMedGoogle Scholar
  35. 35.
    Vaux DL, Cory S, Adams J. Bcl-2 promotes haemopoietic cell survival and cooperates with c-myc to immortalise pre-beta cells. Nature 1988; 335: 440–2PubMedGoogle Scholar
  36. 36.
    Boise LH, Gonzalez-Garcia M, Postema CE, et al. bcl-x, a bcl-2 related gene that functions as a dominant regulator of apoptosis death. Cell 1993; 74: 597–608PubMedGoogle Scholar
  37. 37.
    Muchmore SW, Sattler M, Liang H, et al. X-ray and NMR structure of human bcl-x, an inhibitor of programmed cell death. Nature 1996; 381: 335–41PubMedGoogle Scholar
  38. 38.
    Minn AJ, Velez P, Schendek SL, et al. Bcl-xL forms on ion channel in synthetic lipid membranes. Nature 1997; 385: 353–7PubMedGoogle Scholar
  39. 39.
    Lefebre S, Burglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy determining gene. Cell 1995; 80: 155–65Google Scholar
  40. 40.
    Anderson GP. Resolution of chronic inflammation by therapeutic induction of apoptosis. Trends Pharmacol Sci 1996; 17(12): 438–42PubMedGoogle Scholar
  41. 41.
    Ashwell JD., Berger NA, Cidlowski JA, et al. Coming to terms with death: apoptosis in cancer and immune development. Immunol Today 1994; 15(4): 147–51PubMedGoogle Scholar
  42. 42.
    Vogelstein B. A deadly inheritance. Nature 1990; 348: 681–2PubMedGoogle Scholar
  43. 43.
    Bardeesy N, Beckwith JB, Perretier J. Clonal expansion and attenuated apoptosis in Wilms’ tumour are associated with p53 mutations. Cancer Res 1995; 55: 215–9PubMedGoogle Scholar
  44. 44.
    Newcomb EW. p53 gene mutations in lymphoid diseases and their possible relevance to drug resistance. Leuk Lymphoma 1995; 17: 211–21PubMedGoogle Scholar
  45. 45.
    Iwadate Y, Fujimoto S, Tagawa M, et al. Association of p53 gene mutation with decreased chemosensitivity in human gliomas. Int J Cancer 1996; 69(3): 236–40PubMedGoogle Scholar
  46. 46.
    Evan GI, Wyllie AH, Gilbert CS, et al. Induction of apoptosis in fibroblasts by c-myc protein. Cell 1992; 69: 119–28PubMedGoogle Scholar
  47. 47.
    Anderson GP. Bcl-2 related proteins, apoptosis and disease [comment]. Trends Pharmacol Sci 1997; 18: 51PubMedGoogle Scholar
  48. 48.
    Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science 1995; 267: 1456–62PubMedGoogle Scholar
  49. 49.
    Watson AJM. Necrosis and apoptosis in the gastointestinal tract. Gut 1995; 37: 165–7PubMedGoogle Scholar
  50. 50.
    Merritt AJ, Potten CS, Kemp CJ, et al. The role of p53 in spontaneous and radiation induced apoptosis in the gastrointestinal tract of normal and p53 deficient mice. Cancer Res 1994; 54: 614–7PubMedGoogle Scholar
  51. 51.
    Bursch W, Oberhammer F, Schulte-Hermann R. Cell death by apoptosis and its protective role in disease. Trends Pharmacol Sci 1992; 13(6): 245–51PubMedGoogle Scholar
  52. 52.
    Mullauer I, Grasl-Kraupp B, Bursch W, et al. Transforming growth factor beta-1 induced cell death in preneoplastic foci of rat liver and sensitization by the anti-estrogen tamoxifen. Hepatology 1996; 23(4): 840–7PubMedGoogle Scholar
  53. 53.
    Sugarman PR, Joseph BK, Savage NW. The role of oncogenes, tumour suppressor genes and growth factors in oral squamous cell carcinoma: a case of apoptosis vs proliferation. Oral Dis 1995; 1: 172–88Google Scholar
  54. 54.
    Masunnaga A, Arai T, Yoshitake T, et al. Reduced expression of apoptosis-related antigens in thymuses from patients with myasthenia gravis. Immunol Lett 1994; 39(2): 169–72Google Scholar
  55. 55.
    Aringer M, Wintersberger W, Steiner CW, et al. High levels of bcl-2 protein in circulating T lymphocytes, but not B lymphocytes, of patients with systemic lupus erythematosus. Arthritis Rheum 1994; 37(10): 1423–30PubMedGoogle Scholar
  56. 56.
    Woolley KL, Gibson PG, Carty K, et al. Eosinophil apoptosis and the resolution of airway inflammation in asthma. Am J Respir Crit Care Med 1996; 154: 237–43PubMedGoogle Scholar
  57. 57.
    Lee FD. Importance of apoptosis in the histopathology of drug related lesions in the large intestine. J Clin Pathol 1993; 46(2): 118–22PubMedGoogle Scholar
  58. 58.
    Grigg JM, Savill JS, Sarraf C, et al. Neutrophil apoptosis and clearance from neonatal lungs. Lancet 1991; 338: 720–2PubMedGoogle Scholar
  59. 59.
    Gagliardini V, Hannes P, Drexler CA, et al. Prevention of vertebrate neuronal death by the crm A gene. Science 1994; 263: 826–8PubMedGoogle Scholar
  60. 60.
    Pantaleo G, Graziosi C, Fauci AS. The immunopathogenesis of human immunodeficiency virus infection. N Engl J Med 1993; 328: 327–32PubMedGoogle Scholar
  61. 61.
    Ameisen JC, Capron A. Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis. Immunol Today 1991; 12(4): 102–5PubMedGoogle Scholar
  62. 62.
    Terai C, Kornbluth RS, Pauza CD, et al. Apoptosis as a mechanism of cell death in cultured T lymphocytes acutely infected with HIV-1. J Clin Invest 1991; 87: 1710–4PubMedGoogle Scholar
  63. 63.
    Gschwind M, Huber G. Apoptotic cell death induced by beta-amyloid 1–42 peptide is cell type dependent. J Neurochem 1995; 65(1): 292–300PubMedGoogle Scholar
  64. 64.
    Festoff BW. Amyotrophic lateral sclerosis: current and future treatment strategies. Drugs 1996; 51(1): 28–44PubMedGoogle Scholar
  65. 65.
    Walkinshaw G, Waters CM. Induction of apoptosis in catecholaminergic PC12 cells by L-DOPA: implications for the treatment of Parkinson’s disease. J Clin Invest 1995; 95(6): 2458–64PubMedGoogle Scholar
  66. 66.
    Dipasquale B, Marini AM, Youle RJ. Apoptosis and DNA degradation induced by 1-methyl-4-phenylpyridinium in neurons. Biochem Biophys Res Commun 1991; 181(3); 1442–8PubMedGoogle Scholar
  67. 67.
    Portera-Cailliau C, Sung CH, Nathans J, et al. Apoptotic photoreceptor cell death in mouse models of retinitis pigmentosa. Proc Natl Acad Sci USA 1994; 91(3): 974–8PubMedGoogle Scholar
  68. 68.
    Pollard H, Cantagrel S, Charriaut MC, et al. Apoptosis associated DNA fragmentation in epileptic brain damage. Neuroreport 1994; 5(9): 1053–5PubMedGoogle Scholar
  69. 69.
    Freund G. Apoptosis and gene expression: perspectives on alcohol induced brain damage. Alcohol 1994: 11(5): 385–7PubMedGoogle Scholar
  70. 70.
    Cartwright MM, Smith SM. Increased cell death and reduced neural crest cell numbers in ethanol-exposed embryos: partial basis for the fetal alcohol syndrome phenotype. Alcohol Clin Exp Res 1995; 19(2): 378–86PubMedGoogle Scholar
  71. 71.
    Selleri C, Maciejewski JP, Sato T, et al. Interferon gamma constitutively expressed in the stromal microenvironment of human marrow cultures mediates potent haemopoietic inhibition. Blood 1996; 87(10): 4149–57PubMedGoogle Scholar
  72. 72.
    Laurence J, Mitra D, Steiner M, et al. Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia. J Clin Invest 1996; 97(3): 672–80PubMedGoogle Scholar
  73. 73.
    Yuan J, Angelucci E, Lucarelli G, et al. Accelerated programmed cell death (apoptosis) in erythroid precursors of patients with severe beta-thalassemia (Cooley’s Anemia). Blood 1993: 82(2): 374–7PubMedGoogle Scholar
  74. 74.
    Efferth TH, Fabry U, Glatte P, et al. Increased induction of apoptosis in mononuclear cells of a G6PD deficient patient. J Mol Med 1995: 73(1): 47–9PubMedGoogle Scholar
  75. 75.
    Hatfill BJ, Fester ED, Steytler JG. Apoptotic megakaryocyte dysplasia in the myelodysplastic syndrome. Hematol Pathol 1992: 6(2): 87–92PubMedGoogle Scholar
  76. 76.
    Home WI, Tsukamoto H. Dietary modulation of alcohol induced pancreatic injury. Alcohol 1993; 10(6): 481–4Google Scholar
  77. 77.
    Katz AM. The cardiomyopathy of overload: an unnatural growth response. Eur Heart J 1995; 16 Suppl. O: 110–4PubMedGoogle Scholar
  78. 78.
    Lam TT, Fu J, Hrynewycz M, et al. The effect of aurintricarboxylic acid, an endonuclease inhibitor, on ischemia/ reperfusion damage in rat retina. J Ocul Pharmacol Ther 1995; 11: 253–9PubMedGoogle Scholar
  79. 79.
    Kischer CW. The microvessels in hypertrophie scars, keloids and related lesions: a review. J Submicrosc Cytol Pathol 1992; 24(2): 281–96PubMedGoogle Scholar
  80. 80.
    James TN, Terasaki F, Pavlovich ER, et al. Apoptosis and pleomorphic micromitochondriosis in the sinus nodes surgically excised from five patients with the long QT syndrome. J Lab Clin Med 1993: 122(3): 309–23PubMedGoogle Scholar
  81. 81.
    Kwo P, Patel T, Bronk SF, et al. Nuclear serine protease activity contributes to bile acid-induced apoptosis in hepatocytes. Am J Physiol 1995: 268: G613–21PubMedGoogle Scholar
  82. 82.
    Zalewski PD, Forbes IJ, Betts WH. Correlation of apoptosis with change in intracellular labile Zn (II) using zinquin. Biochem J 1993; 296: 403–8PubMedGoogle Scholar
  83. 83.
    Seigers C-P. Anthranoid laxatives and colorectal cancer. Trends Pharmacol Sci 1992; 13(6): 229–31Google Scholar
  84. 84.
    Geboes K, Spiessens C, Nijs G, et al. Anthranoids and the mucosal immune system of the colon. Pharmacology 1993; 47: 49–57PubMedGoogle Scholar
  85. 85.
    Walker NI, Bennett RE, Axelsen RA. Melanosis coli a consequence of anthraquinone induced apoptosis of colonic epithelial cells. Am J Pathol 1988; 131: 465–76PubMedGoogle Scholar
  86. 86.
    Holmgren L, O’Reilly MS, Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1995; 1(2): 149–53PubMedGoogle Scholar
  87. 87.
    Kyprianou N. Apoptosis: therapeutic significance in the treatment of androgen dependent and androgen independent prostate cancer. World J Urology 1994; 12(6): 299–303Google Scholar
  88. 88.
    Baral E, Nagy E, Berczi I. Modulation of natural killer cell mediated cytotoxicity by tamoxifen and estradiol. Cancer 1995; 75(2): 591–9PubMedGoogle Scholar
  89. 89.
    Kang Y, Cortina R, Perry RR. Role of c-myc in tamoxifen-induced apoptosis in estrogen independent breast cancer cells. J Natl Cancer Inst 1996; 88(5): 279–84PubMedGoogle Scholar
  90. 90.
    Perry RR, Kang Y, Greaves BR. Relationship between tamoxifen induced transforming growth factor beta 1 expression, cytostasis and apoptosis in human breast cancer cells. Br J Cancer 1995; 72: 1441–6PubMedGoogle Scholar
  91. 91.
    Iwasaki K, Toms SA, Barnett GH, et al. Inhibitory effects of tamoxifen and tumour necrosis factor alpha on human glioblastoma cells. Cancer Immunol Immunother 1995; 40(4): 228–34PubMedGoogle Scholar
  92. 92.
    Yano T, Korkut E, Pinski J, et al. Inhibition of growth of MCF-7 MIII human breast carcinoma in nude mice by treatment with agonists or antagonists of LH-RH. Breast Cancer Res Treat 1992; 21(1): 35–45PubMedGoogle Scholar
  93. 93.
    Kleinman D, Douvdeyani A, Schally AV, et al. Direct growth inhibition of human endometrial cancer cells by the gonadotropin-releasing hormone antagonist SB-75; role of apoptosis. Am J Obstet Gynecol 1994; 170: 96–102PubMedGoogle Scholar
  94. 94.
    Szepeshazi K, Lapis K, Schally AV. Effect of combination treatment with analogs of LHRH or somatostatin and 5FU on pancreatic cancer in hamsters. Int J Cancer 1991; 49(2): 260–6PubMedGoogle Scholar
  95. 95.
    Smets LA, van den Berg JD. Bcl-2 expression and gluco-corticoid induced apoptosis of leukemic cells and lymphoma cells. Leuk Lymphoma 1996; 20: 199–205PubMedGoogle Scholar
  96. 96.
    Alnemri ES, Fernandes TF, Haldar S, et al. Involvement of bcl2 in glucocorticoid induced apoptosis in pre-B-leukemias. Cancer Res 1992; 52(2): 491–5PubMedGoogle Scholar
  97. 97.
    Shwartzman RA, Cidlowsky JA. Mechanism of tissue specific induction of internucleosomal DNA cleavage activity and apoptosis by glucocorticoids. Endocrinology 1993; 133(2): 591–9Google Scholar
  98. 98.
    McConkey DJ, Orrenius S, Okret S, et al. cAMP potentiates the glucocorticoid induced endonuclease activation in thymocytes. FASEB J 1993; 7(6): 580–5PubMedGoogle Scholar
  99. 99.
    Brach MA, d Vos S, Gruss HJ, et al. Prolongation of survival of human PMN by GM-CSF is caused by inhibition of programmed cell death. Blood 1992; 80: 2920–4PubMedGoogle Scholar
  100. 100.
    Bergamaschi G, Rosti V, Danova M, et al. Inhibitors of tyrosine phosphorylation induces apoptosis in human leukemic cell lines. Leukemia 1993; 7(12): 2012–8PubMedGoogle Scholar
  101. 101.
    Collins MK, Marvel J, Malde P, et al. IL-3 protects bone marrow cells from apoptosis induced by DNA damaging agents. J Exp Med 1992; 176(4): 1043–51PubMedGoogle Scholar
  102. 102.
    Usha D, Thatte UM, Dahanukar SA. Therapeutic potential of the hemopoietic growth factors. J Postgrad Med 1994; 40(4): 210–5PubMedGoogle Scholar
  103. 103.
    Kaplinksky C, Lotem J, Sachs L. Protection of human myeloid leukemia cells against doxorubicin-induced apoptosis by granulocyte-macrophage colony stimulating factor and interleukin-3. Leukemia 1996; 10(3): 460–5Google Scholar
  104. 104.
    Bessho M, Yoshida S, Sakate K, et al. Suppression of the development of murine myeloid leukemia with granulocyte colony stimulating factor by inducing apoptosis of leukemic cells. Leukemia 1994; 8(7): 1185–90PubMedGoogle Scholar
  105. 105.
    Bhalla K, Tang C, Ibrado AM, et al. GM-CSF/IL-3 fusion protein (pIXY 321) enhances high dose Ara-C induced programmed cell death or apoptosis in human myeloid leukemia cells. Blood 1992; 80(11): 2883–90PubMedGoogle Scholar
  106. 106.
    Tang C, Huang Y, Ponnathpur VS, et al. Combined antileukemic activity of pIXY 321 and Ara-C against human acute myeloid leukemia cells. Leuk Lymphoma 1994; 15: 445–51PubMedGoogle Scholar
  107. 107.
    Fluckiger AC, Durand I, Banchereau J. Interleukin 10 induces apoptotic cell death of B-chronic lymphocytic leukemia cells. J Exp Med 1994; 179(1): 91–9PubMedGoogle Scholar
  108. 108.
    Capelli E, Barni S, Vaccarone R, et al. Cell activation and death (apoptosis) induced by IL-2: ultrastructural evidence. Anti-cancer Res 1996; 16: 1775–80Google Scholar
  109. 109.
    Novelli P, Garotta G, Forni G. Environmental signals influencing expression of the IFN-gamma receptor on human T cells control whether IFN-gamma promotes proliferation or apoptosis. J Immunol 1994; 152(2): 496–504PubMedGoogle Scholar
  110. 110.
    Kitabayashi A, Hirokawa M, Miura AB. The role of interleukin-10 (IL-10) in chronic B-lymphocytic leukemia: IL-10 prevents leukemic cells from apoptotic cell death. Int J Haematol 1995; 62: 99–106Google Scholar
  111. 111.
    Tisman G, Show-Jen GW. Lithium-induced leucocytosis. Lancet 1977; II: 251–2Google Scholar
  112. 112.
    Mediehe AM, Mampuru LJ, Tyobeka EM. Induction of apoptosis in HL-60 cells by lithium. Biochem Biophys Res Commun 1995; 209(2): 768–74Google Scholar
  113. 113.
    Wood AC, Elvin P, Hickman JA. Induction of apoptosis by anti-cancer drugs with disparate modes of action: kinetics of cell death and changes in c-myc expression. Br J Cancer 1995; 71(5): 937–41PubMedGoogle Scholar
  114. 114.
    Neubauer A, Thiede C, Huhn D, et al. p53 and induction of apoptosis as a target for anticancer treatment. Leukemia 1996; 10(3): 52–4Google Scholar
  115. 115.
    Stoetzer OJ, Nussler V, Darsow M, et al. Association of bcl-2, bax, bcl-xL, IL-1 beta converting enzyme expression with initial response to chemotherapy treatment in acute myeloid leukemia. Leukemia 1996; 10(S3): 318–22Google Scholar
  116. 116.
    Maung ZT, MacLean FR, Reid MM, et al. The relationship between bcl-2 expression and response to chemotherapy in acute leukemia. Br J Haematol 1994; 88: 105–9PubMedGoogle Scholar
  117. 117.
    Segal-Bendirdjian E, Jacquemin-Sablon A. Cisplatin resistance in a murine leukemia cell line is associated with a defective apoptotic process. Exp Cell Res 1995; 218(1): 201–12PubMedGoogle Scholar
  118. 118.
    Benhatter J, Cerottini JP, Saraga E, et al. p53 mutations as a possible predictor of response to chemotherapy in metastatic colorectal carcinomas. Int J Cancer 1996; 69(3): 190–2Google Scholar
  119. 119.
    Gruber J, Greil R. Apoptosis and therapy of malignant diseases of the hematological system. Int Arch Allergy Immunol 1994; 105: 368–73PubMedGoogle Scholar
  120. 120.
    Kondo S, Yin D, Takeuchi J, et al. Bcl2 gene enables rescue from in vitro myelosuppression (bone marrow cell death) induced by chemotherapy. Br J Cancer 1994; 70: 421–6PubMedGoogle Scholar
  121. 121.
    Singh N. Apoptotic cell death and cancer therapy. Drugs: News and Views 1994Google Scholar
  122. 122.
    Gillio-Tos A, Cignetti A, Rovera G, et al. Retroviral vector-mediated transfer of the tumour necrosis factor alpha gene into human cancer cells restores an apoptotic cell death program and induces a bystander-killing effect. Blood 1996; 87: 2486–95PubMedGoogle Scholar
  123. 123.
    Jones KD, Couldwell WT, Hinton DR, et al. Lovastatin induces growth inhibition and apoptosis in human malignant glioma cell lines. Biochem Biophys Res Commun 1994; 205(3): 1681–7PubMedGoogle Scholar
  124. 124.
    Cotter TG. Programmed to die: cell death in the immune system. Immunologist 1993; 1(6): 181–4Google Scholar
  125. 125.
    Vaux DL. Toward an understanding of the molecular mechanisms of physiological cell death. Proc Natl Acad Sci USA 1993; 90: 786–9PubMedGoogle Scholar
  126. 126.
    Emlen W, Niebur J, Kadera R. Accelerated in vitro apoptosis of lymphocytes from patients with systemic lupus erythematosus. J Immunol 1994; 152(7): 3685–92PubMedGoogle Scholar
  127. 127.
    Mountz JD, Wu J, Cheng J, et al. Autoimmune disease: a problem of defective apoptosis. Arthritis Rheum 1994; 37(10): 1415–20PubMedGoogle Scholar
  128. 128.
    Zetti UK, Gold R, Toyka KV, et al. Intravenous glucocorticoid treatment augments apoptosis of inflammatory T cells in experimental autoimmune neuritis. J Neuropathol Exp Neurol 1995; 54(4): 540–7Google Scholar
  129. 129.
    Spinozzi F, Agea E, Bistoni O, et al. T lymphocytes bearing the gamma delta T cell receptor are susceptible to steroid induced programmed cell death. Scand J Immunol 1995; 41: 504–8PubMedGoogle Scholar
  130. 130.
    Racke MK, Critchfield ZM, Quigley L, et al. Intravenous antigen administration as a therapy for autoimmune demyelinating disease. Ann Neurology 1996; 39: 46–56Google Scholar
  131. 131.
    Suzuki S, Okubo M, Kaise S, et al. Gold sodium thiomalate selectively inhibits IL-5 mediated eosinophils. J Allergy Clin Immunol 1995; 96(2): 251–6PubMedGoogle Scholar
  132. 132.
    Miesel R, Kurpisz M, Kroger H. Modulation of inflammatory arthritis by inhibition of poly (ADP ribose) polymerase. Inflammation 1995; 19: 379–87PubMedGoogle Scholar
  133. 133.
    Fadok VA, Savill JS, Haslett C, et al. Different populations of macrophages use either the vitronectin receptor or the phosphatidylserine receptor to recognise and remove apoptotic cells. J Immunol 1992; 149(12): 4029–35PubMedGoogle Scholar
  134. 134.
    Zhang YH, Takahashi K, Jiang GZ, et al. In vivo induction of apoptosis (programmed cell death) in mouse thymus by administration of lipopolysaccharide. Infect Immun 1993; 61(12): 5044–8PubMedGoogle Scholar
  135. 135.
    Mangan DF, Mergenhagen SE, Wahl SM. Apoptosis in human monocytes: possible role in chronic inflammatory diseases. J Periodontol 1993; 64: 461–6PubMedGoogle Scholar
  136. 136.
    Mannick EE, Bravo IE, Zarama G, et al. Inducible nitric oxide synthase, nitrotyrosine and apoptosis in Helicobacter pylori gastritis: effect of antibiotics and antioxidants. Cancer Res 1996; 56(14): 3238–43PubMedGoogle Scholar
  137. 137.
    Umehara F, Nakamura A, Izumo S, et al. Apoptosis of T lymphocytes in the spinal cord lesions in HTLV-I associated myelopathy: a possible mechanism to control viral infection in the central nervous system. J Neuropathol Exp Neurol 1994; 53(6): 617–24PubMedGoogle Scholar
  138. 138.
    Cox G. Glucocorticoid treatment inhibits apoptosis in human neutrophils. Separation of survival and activation outcomes. J Immunol 1995; 154(9): 4719–25PubMedGoogle Scholar
  139. 139.
    Aoshiba K, Nagai A, Konno K. Erythromycin shortens neutrophil survival by accelerating apoptosis. Antimicrob Agents Chemother 1995; 39(4): 872–7PubMedGoogle Scholar
  140. 140.
    Lu X, Xie W, Reed D, et al. NSAIDs cause apoptosis and induce cyclooxygenase in chicken fibroblasts. Proc Natl Acad Sci USA 1995; 92: 7961–5PubMedGoogle Scholar
  141. 141.
    Akbar AN, Salmon M, Janossy G. Role of bcl-2 and apoptosis in viral infections. Int Arch Allergy Immunol 1994; 105(4): 359–62PubMedGoogle Scholar
  142. 142.
    Akbar AN, Savill J, Gombert W, et al. The specific recognition by macrophages of CD8+, CD45RO+ T cells undergoing apoptosis: a mechanism for T cell clearance during resolution of viral infections. J Exp Med 1994; 180(5): 1943–7PubMedGoogle Scholar
  143. 143.
    Groux H, Torpier G, Monte D, et al. Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals. J Exp Med 1992; 175: 331–40PubMedGoogle Scholar
  144. 144.
    Banda NK, Berrier J, Kurahara DK, et al. Crosslinking CD4 by human immunodeficiency virus gp 120 primes T cells for activation induced apoptosis. J Exp Med 1992; 38: 252–6Google Scholar
  145. 145.
    Mitra D, Steiner M, Lynch DH, et al. HIV-1 upregulates Fas ligand expression in CD4+ T cells in vitro and in vivo: association with Fas-mediated apoptosis and modulation by aurintricarboxylic acid. Immunology 1996; 87: 581–5PubMedGoogle Scholar
  146. 146.
    Finkel TH, Tudor WG, Banda NK, et al. Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV and SIV infected lymph nodes. Nat Med 1995; 1(2): 129–34PubMedGoogle Scholar
  147. 147.
    Famularo G, De Simone C. A new era for carnitine? Immunol Today 1995; 16(5); 211–3PubMedGoogle Scholar
  148. 148.
    Huss R, Hoy CA, Ottinger H, et al. Cyclosporine induced apoptosis in CD4+ T lymphocytes and computer simulated analysis: modeling a treatment scenario for HIV infection. Res Immunol 1995; 146(2): 101–8PubMedGoogle Scholar
  149. 149.
    Thomson AW, Bonham CA. Inhibition of T lymphocyte activation and apoptotic cell death by cyclosporin A and tacrolimus (FK 506): its relevance to therapy of HIV infection. Adv Exp Med Biol 1995; 374: 211–6PubMedGoogle Scholar
  150. 150.
    Lu W, Salerno-Goncalves R, Yuan J, et al. Glucocorticoids rescue CD4+ T lymphocytes from activation induced apoptosis triggered by HIV-1: implications for pathogenesis and therapy. AIDS 1995; 9: 35–42PubMedGoogle Scholar
  151. 151.
    Yang Y, Bailey J, Vacchio MS, et al. Retinoic acid inhibition of ex vivo human immunodeficiency virus associated apoptosis of peripheral blood cells. Proc Natl Acad Sci USA 1995; 92(7): 3051–5PubMedGoogle Scholar
  152. 152.
    Forloni G, Chiesa R, Smiroldo S, et al. Apoptosis mediated neurotoxicity induced by chronic application of beta amyloid fragment 25–35. Neuroreport 1993; 4(5): 523–6PubMedGoogle Scholar
  153. 153.
    Branconnier RJ, Branconnier ME, Walshe TM, et al. Blocking the Ca (2+) activated cytotoxic mechanisms of cholinergic neuronal death: a novel treatment strategy for Alzheimer’s disease. Psychopharmacol Bull 1992; 28(2): 175–8PubMedGoogle Scholar
  154. 154.
    Fang J, Zuo DM, Yu PH. Lack of protective effect of R (()-deprenyl on programmed cell death of mouse thymocytes induced by dexamethasone. Life Sci 1995; 57(1): 15–22PubMedGoogle Scholar
  155. 155.
    Mitchell IJ, Lawson S, Moser B, et al. Glutamate-induced apoptosis results in a loss of striatal neurons in the parkinsonian rat. Neuroscience 1994; 63(1): 1–5PubMedGoogle Scholar
  156. 156.
    Walkinshaw G, Waters CM. Neurotoxin-induced cell death in neuronal PC12 cells is mediated by induction of apoptosis. Neuroscience 1994; 63(4): 975–87PubMedGoogle Scholar
  157. 157.
    Bonfoco E, Krainc D, Ankarcrona M, et al. Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical cell cultures. Proc Natl Acad Sci USA 1995; 92(16): 7162–6PubMedGoogle Scholar
  158. 158.
    Neff NT, Prevette D, Houenou LJ, et al. Insulin-like growth factors: putative muscle-derived trophic agents that promote motoneuron survival. J Neurobiol 1993; 24(12): 1578–88PubMedGoogle Scholar
  159. 159.
    Ferrari G, Yan CY, Greene LA. N-acetylcysteine (D- and L-stereoisomers) prevents apoptotic death of neuronal cells. J Neurosci 1995; 15(4): 2857–66PubMedGoogle Scholar
  160. 160.
    Garcia I, Martinou I, Tsujimoto Y, et al. Prevention of programmed cell death of sympathetic neurons by bcl-2 protooncogene. Science 1992; 258: 302–4PubMedGoogle Scholar
  161. 161.
    Vaux DL, Wacker G. Hypothesis: apoptosis caused by cytotoxins represents a defensive response that evolved to combat intracellular pathogens. Clin Exp Pharmacol Physiol 1995; 22: 861–3PubMedGoogle Scholar
  162. 162.
    Patel T, Gores GJ. Apoptosis and hepatobiliary disease. Hepatology 1995; 21(6): 1725–41PubMedGoogle Scholar
  163. 163.
    Goldin RD, Hunt NC, Clark J, Wickramsinghe SN. Apoptotic bodies in a murine model of alcoholic liver disease: reversibility of ethanol-induced changes. J Pathol 1993; 171(1): 73–6PubMedGoogle Scholar
  164. 164.
    Cascales M, Alvarez A, Gasco P, et al. Cocaine-induced liver injury in mice elicits specific changes in DNA ploidy and induces programmed death of hepatocytes. Hepatology 1994; 20: 992–1001PubMedGoogle Scholar
  165. 165.
    Woo D. Apoptosis and loss of renal tissue in polycystic kidney diseases. N Engl J Med 1995; 333: 18–25PubMedGoogle Scholar
  166. 166.
    Morgan MG, Cable HC, Newcombe NR, et al. Treatment of culture pancreatic beta cells with streptozotocin induces cell death by apoptosis. Biosci Rep 1994; 14(4): 243–50PubMedGoogle Scholar
  167. 167.
    Mustoe TA, Pierce G. Pharmacologic enhancement of wound healing. Ann Rev Med 1995; 46: 467–81PubMedGoogle Scholar
  168. 168.
    Chen GO, Zhu J, Shi XG, et al. In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As203) in the treatment of acute promyelocytic leukemia: As203 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood 1996 Aug 1; 88(3): 1052–61PubMedGoogle Scholar
  169. 169.
    Li L, Nevill G, Forge A. Two modes of hair cell loss from the vestibular sensory epithelia of the guinea pig inner ear. J Comp Neurol 1995; 355(3): 405–17PubMedGoogle Scholar
  170. 170.
    Kimura S, Maekawa T, Hirakawa K, et al. Alterations of c-myc expression by antisense oligodeoxynucleotides enhance the induction of apoptosis in HL-60 cells. Cancer Res 1995; 55(6): 1379–84PubMedGoogle Scholar
  171. 171.
    Leonetti C, D’Agnano I, Lo-zupone F, et al. Antitumour effect of c-myc antisense phosphorothioate oligodeoxynucleotides on human melanoma cells in vitro and in mice. J Natl Cancer Inst 1996; 88: 419–29PubMedGoogle Scholar
  172. 172.
    Smith MR, Abubakr Y, Mohammad R, et al. Antisense oligodeoxyribonucleotide down regulation of bcl-2 gene expression inhibits growth of the low grade non-Hodgkin’s lymphoma cell line WSH-FSCCL. Cancer Gene Therapy 1995; 2(3): 207–12PubMedGoogle Scholar
  173. 173.
    Kuo CL, Chou CC, Yung BY. Berberine complexes with DNA in the berberine induced apoptosis in human leukemic HL-60 cells. Cancer Lett 1995; 93(2): 193–200PubMedGoogle Scholar
  174. 174.
    Hughes DE, Wright KR, Uy HL, et al. Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 1995; 10(10): 1478–87PubMedGoogle Scholar
  175. 175.
    Mentz F, Merle-Boral H, Ouaazf F, et al. Theophylline, a new inducer of apoptosis in B-CC1: role of cyclic nucleotides. Br J Haematol 1995; 90: 957–9PubMedGoogle Scholar
  176. 176.
    Robertson CN, Robertson KM, Padilla GM, et al. Induction of apoptosis by diethylstilbestrol in hormone insensitive prostate cancer cells. J Natl Cancer Inst 1996 Jul 3; 88(13): 908–17PubMedGoogle Scholar
  177. 177.
    Rittmaster RS, Norman RW, Thomas IN, et al. Evidence for atrophy and apoptosis in the prostates of given finasteride. J Clin Endocrinol Metab 1996; 81(2): 814–9PubMedGoogle Scholar
  178. 178.
    Abou-Rabia L, Kendall MD. Involution of the rat thymus in experimentally induced hypothyroidism. Cell Tissue Res 1994; 277(3): 447–55PubMedGoogle Scholar
  179. 179.
    Traganos F, Kapuscinski J, Gong J, et al. Caffeine prevents apoptosis and cell cycle effects induced by camptothecin or topotecan in HL-60 cells. Cancer Res 1993; 53(19): 4613–8PubMedGoogle Scholar
  180. 180.
    Belizario JE, Tilly JL, Sherwood SW. Caffeine potentiates the lethality of tumor necrosis factor in cancer cells. Br J Cancer 1993; 67(6): 1229–35PubMedGoogle Scholar
  181. 181.
    Ray SD, Kamendulus LM, Gurule MW, et al. Ca2+ antagonists inhibit DNA fragmentation and toxic cell death induced by acetaminophen. FASEB J 1993; 7: 453–63PubMedGoogle Scholar
  182. 182.
    Pahor M, Guralnik JM, Ferrucci L, et al. Calcium channel blockade and incidence of cancer in aged populations. Lancet 1996; 348: 493–7PubMedGoogle Scholar
  183. 183.
    Jick H, Jick S, Derby LE, et al. Calcium channel blockers and risk of cancer. Lancet 1997; 349: 525–8PubMedGoogle Scholar
  184. 184.
    Kondo S, Yin D, Morimura T, et al. Combination therapy with cisplatin and nifedipine inducing apoptosis in multidrug-resistant human glioblastoma cells. J Neurosurg 1995; 82: 469–74PubMedGoogle Scholar
  185. 185.
    Boolbol SK, Dannenberg AJ, Chadburn A, et al. Cyclooxygenase-2 overexpression and tumour formation are blocked by sulindac in a murine model of familial adenomatous polyposis. Cancer Res 1996; 56(11): 2556–60PubMedGoogle Scholar
  186. 186.
    Pasricha PJ, Bedi A, O’Connor K, et al. The effects of sulindac on colorectal proliferation and apoptosis in familial adenomatous polyposis. Gastroenterology 1995; 109(3): 994–8PubMedGoogle Scholar
  187. 187.
    Indap MA, Rao SGA. Cell death by apoptosis and cancer chemotherapy. Natl Med J India 1995; 8(2); 65–7PubMedGoogle Scholar
  188. 188.
    Bussing A, Suzart K, Bergmann J, et al. Induction of apoptosis in human lymphocytes treated with viscum album L is mediated by the mistletoe lectins. Cancer Lett 1996; 99: 59–72PubMedGoogle Scholar
  189. 189.
    Thatte UM, Dahanukar SA. Comparative study of immunomodulating activity of Indian medicinal plants, lithium carbonate and glucan. Methods Find Exp Clin Pharm 1988; 10: 639–44Google Scholar
  190. 190.
    Thatte UM, Dahanukar SA. Immunotherapeutic modification of diverse infectious states by Indian medicinal plants. Phytotherapy Res 1989; 3(2): 43–9Google Scholar
  191. 191.
    Thatte UM, Dahanukar SA, Rao SGA. Tinospora cordifolia induces production of GM-CSF. J Postgrad Med 1994; 40(4): 202–3PubMedGoogle Scholar
  192. 192.
    Maneckgee R, Minna JD. Opioids induce while nicotine suppresses apoptosis in human lung cancer cells. Cell Growth Differ 1994; 5: 1033–40Google Scholar
  193. 193.
    Grindley J. Apoptosis — death under review. Scrip 1994 Jul/Aug; 42–5Google Scholar
  194. 194.
    Akhtar S, Agrawal S. In vivo studies with antisense oligonucleotides. Trends Pharmacol Sci 1997; 18(1): 12–8PubMedGoogle Scholar
  195. 195.
    Nicotera P, Brune B, Bagetta G. Nitric oxide: inducer or suppressor of apoptosis? Trends Pharmacol Sci 1997; 18(6): 189–90PubMedGoogle Scholar
  196. 196.
    Olivetti G, Abbi R, Quaini F, et al. Apoptosis in the human heart. N Engl J Med 1997; 336: 1131–41PubMedGoogle Scholar

Copyright information

© Adis International Limited 1997

Authors and Affiliations

  1. 1.Department of PharmacologySeth GS Medical CollegeParel MumbaiIndia

Personalised recommendations