Steven Grant.

Division of hermatology , Department of Pharmacology and Microbiology , Medical College of Virginia

Received 5/23/97; Accepted 5/28/97

9. REFERENCES

1. Wyllie, A.H., Kerr, J.F.R., Currie, A.R. Cell death: the significance of apoptosis. Int. Rev. Cytol. 68, 251-306 (1980)

2. Lotem, J., Cragoe, E., Sachs, L. Rescue from programmed cell death in leukemia and normal cells. Blood 78 , 953-60 (1991).

3. Oberhammer, F., Wilson, J.W., Dive, C., Morris, I.D., Hickman, J.A., Wakeling, A.E., Walker, R.P., Sikorska, M. Apoptotic death in epithelial cells: cleavage of DNA to 300 or 50 kb fragments prior to or in the absence of internucleosomal fragmentation. EMBO J 12, 3679-3684 (1993).

4. Kaufmann S. Induction of endonucleolytic DNA cleavage in human acute myeloid leukemia cells etoposide, camptothecin, and other cytotoxic anticancer drugs: a cautionary note. Cancer Res 48, 5870-5878 (1989).

5. Gorczyca, W., Bigman, K., Mittelman, A., Ahmed, T., Gong, J., Melamed, M.R., Darzynkiewicz, Z. Induction of DNA strand breaks associated with apoptosis during treatment of leukemias. Leukemia 7, 659-70 (1993).

6. Grant, S., Lehman, C., Cadman, E. Enhancement of 1- -D-arabinofuranosylcytosine accumulation within L1210 cells and increased cytotoxicity following thymidine exposure. Cancer Res.40, 1525-1531 (1980).

7. Nishizuka, Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature 308, 693-698 (1984)

8. Grant S, Jarvis D, Swerdlow P, Turner A, Traylor R, Wallace H, Lin, P-S, Pettit GR, Gewirtz DA: Potentiation of the activity of 1- -D-arabinofuranosylcytosine by the macrocyclic lactone PKC activator bryostatin 1 is associated with enhanced fragmentation of mature DNA. Cancer Res 52, 6270-78 (1992)

9. Jarvis WD, Gewirtz DA, Povirk L, Turner A, Traylor R, Pettit GR, Grant S: Effect of bryostatin 1 and other activators of protein kinase C on 1--D-arabinofuranosylcytosine-induced apoptosis in HL-60 human promyelocytic leukemia cells. Biochem Pharmacol 47, 839-52 (1994)

10. Mastrianni, D.M., Tung, N.M., Tenen, D.G. Acute myelogenous leukemia: current treatment and future directions. Am. J. Med. 82, 286-295 (1992)

11. Plagemann, P.G.W., Marz, R., Wolheuter, R.M. Transport and metabolism of deoxycytidine and 1--D-arabinofuranosylcytosine into cultured Novikoff rat hepatoma cells, relationship to phosphorylation, and regulation of triphosphate synthesis. Cancer Research 38, 978-989 (1978)

12. Durham, J.P., Ives, D.H. Deoxycytidine kinase. II. Purification and general properties of the calf thymus enzyme. J. Biol. Chem. 245 , 2276-2284 (1970)

13. Wang, L.M., Kucera, G.L. Deoxycytidine kinase is phosphorylated in vitro by protein kinase C-. Biochim. Biophys. Acta. 1224, 161-167 (1994)

14. Steuart, C.D., Burke, P.J. Cytidine deaminase and the development of resistance to arabinosyl cytosine. Nature New Biol. 233, 109-110 (1971)

15. Furth, J.J., Cohen, S.S. Inhibition of mammalian DNA polymerase by the 5'-triphosphate of 1--D-arabinofuranosylcytosine and the 5'-triphosphate of 1--D-arabinofuranosyladenine. Cancer Res.28, 2061-2067 (1968)

16. Major, P.P., Egan, E., Herrick, D.J., Kufe, D.W. Effect of ara-C incorporation on deoxyribonucleic synthesis in cells. Biochem. Pharmacol. 31, 2937-2940 (1982)

17. Kufe, D.W., Major, P.P., Egan, M., Beardsley, P. Incorporation of ara-C into L1210 DNA as a correlate of cytotoxicity. J. Biol. Chem. 255 , 8997-9000 (1981)

18. Kucera, G.L., Capizzi, R.L. 1--D-arabinofuranosylcytosine-diphosphate-choline is formed by the reversal of cholinephosphotransferase and not via cytidylyltransferase. Cancer Res. 52, 3886-3891(1992)

19. Kharbanda, S., Datta, R., Kufe, D. regulation of c-jun gene expression in HL-60 luekemia cells by 1--D-arabinofuranosylcytosine. Potential involvement of a protein kinase C-dependent mechanism. Biochemistry 30, 7947-7952 (1991)

20. McConkey, D.J., Hartzell, P., Jondal, M., Orrenius, S. Inhibition of DNA fragmentation in thymocytes and isolated thymocyte nuclei by agents that stimulate protein kinase C. J Biol Chem 264, 13399-13402 (1989)

21. Strum, J.C., Small, G.W., Pauig, S.B., Daniel, L.W. 1- -D-arabinofuranosylcytosine stimulates ceramide and diglyceride formation in HL-60 cells. J. Biol. Chem. 269, 15493-15497 (1994)

22. Y.A. Hannun. Functions of ceramide in coordinating cellular responses to stress. Science 274:1855-1858 (1996)

23. Jarvis, W.D., Kolesnick, R.W., Fornari, F.A., Traylor, R.S., Gewirtz, D.A., Grant, S. Activation of the sphingomyelinase pathway initiates apoptosis in a variety of mammalian cell lines. Proc. Natl. Acad. Sci. USA 91, 73-77 (1994)

24. Wiley, J.S., Jones, S.P., Sawyer, W.H., Paterson, A.R.P. Cytosine arabinoside influx and nucleside tranport sites in acute leukemia. J. Clin. Invest. 69, 479-489 (1982)

25. Bhalla, K.R., Nayak, R., Grant, S. Isolation and characterization of a deoxycytidine kinase-deficient human promyelocytic leukemic cell line highly resistant to 1--D-arabinofuranosylcytosine. Cancer Res. 44, 5029-5037 (1984)

26. Steuart, C.D., Burke, P.J. Cytidine deaminase and the development of resistance to arabinosyl cytosine. Nature New Biol. 233, 109-110 (1971).

27. Abe, I., Saito, S., Hori, K., Suzuki, M., Sato, H. Role of dephosphorylation in accumulation of 1--D- arabinofuranolsylcytosine 5'-triphosphate in human lymphoblastic cell lines with reference to their drug sensitivity. Cancer Res. 42, 2846-2851 (1982)

28. de St. Vincent, Buttin, G. Studies on 1--D-arabinofuranosylcytosine-resistant mutants of chinese hamster fibroblasts: II Joint resistance to arabinofuranosyl cytosine and to excess thymidine- a semi-dominant manifestation of deoxycytidine triphosphate pool expansion. Somat. Cell Genet. 5, 162-167 (1979).

29. Major, P.P., Egan, E.M., Beardsley, G.P., Minden, M.E., Kufe, D.W. Lethality of human myeloblasts correlates with the incorporation of arabinofuranosylcytosine int DNA. Proc. Natl. Acad. Sci. USA. 78, 3235-3239 (1981)

30. Miyashita, T., Reed, J.C. Bcl-2 oncoprotein blocks chemotherapy-induced apoptosis in human leukemia cell line. Blood 81, 151-157 (1993)

31. Manome, Y., Weichselbaum, R.R., Kufe, D.W., Fine, H.A. Effect of Bcl-2 on ionizing radiation and 1--D-arabinofuranosylcytosine-induced internucleosomal DNA fragmentation and cell survival in human myeloid leukemia cells. Oncol. Res. 5, 139-144 (1993)

32. Ibrado, A.M., Huang, Y., Fang, G., Liu, L., Bhalla, K. Overexpression of Bcl-2 or Bcl-xL inhibits ara-C-induced CPP32/Yama protease activity and apoptosis of human acute myelogenous leukemia HL-60 cells. Cancer Res. 56, 4743-4748 (1996).

33. Bullock, G., Ray, S., Reed, J.C., Krajewski, S., Ibrado, A.M., Huang, Y., Bhalla, K. Intracellular metabolism of ara-C and resulting DNA fragmentation and apoptosis of human AML HL-60 cells possessing disparate levels of Bcl-2 protein. Leukemia 10, 1731-1741 (1996)

34. Pettit G.R., Herald C.L., Boubek D.L., Herald D.L., Arnold E., Clardy, J.: Isolation and structure of bryostatin 1. J Am Chem Soc 104,6846-6948 (1982)

35. Kennedy, M.J., Prestigiacomo, L.J., Tyler, G., May, W.S., Davidson, N.E. Differential effects of bryostatin 1 and phorbol ester on human breast cancer cell lines. Cancer Res.52,1278-83 (1992).

36. Basu, A., Lazo, J.S. Sensitization of human cervical cancer cells to cis-diamminechloroplatinum(II) by bryostatin 1. Cancer Res.52 , 3119-3124 (1992)

37. Hornung, R.L., Pearson, J.W., Beckwith, M., Longo, D.L. Preclinical evaluation of bryostatin as an anticancer agent against several tumor cell lines: in vitro versus in vivo activity. Cancer Res. 52, 101-107 (1992)

38. L.M. Schucter, A.H. Esa, W.S. May, M.K. Laulis, G.R. Pettit, A.D. Hess. Successful treatment of murine melanoma with bryostatin 1. Cancer Res. 51,682-687 (1991)

39. Jayson, G.C., Crowther, D., Prendiville, J., McGown, A.T., Scheid, C., Stern, P., Young, R., Brenchley, P., Chang, J., Owens, S., Pettit, G.R. A phase I trial of bryostatin 1 in patients with advanced malignancy using a 24 hour intravenous infusion. Br. J. Cancer 72,461-8 (1995)

40. Philip, P., Rea, D., Thavasu, P., Carmichael, J., Stuart, N.S.A., Rockett, H., Talbot, D.C., Ganesan, T., Pettit, G.R., Balkwill, F., Harris, A.L. Phase I study of bryostatin 1: assessment of interleukin-6 and tumour necrosis factor in vivo. J Natl Cancer Inst 85, 1812-1818 (1993)

41. Prendiville J., Crowther D., Thatcher, N., Woll, P.J., Fox, B.W., McGown, A., Stern, P., McDermott, R., Potter, M., Pettit, G.R. A phase I study of intravenous bryostatin 1 in patients with advanced cancer. Br J Cancer 68, 418-424 (1993)

42. Berkow, R.L., Kraft, A.S., Bryostatin, a non-phorbol ester macrocyclic lactone, activates intact human polymorphonuclear leukocytes and binds to the phorbol ester receptor. Biochem. Biophys. Res. Commun. 131, 1109-16 (1985)

43. Drexler, H.G., Gignac, S.M., Jones, R.A., Scott, C.S., Pettit, G.R., Hoffbrand, A.V. Bryostatin 1 induces differentiation of B-chronic lymphocytic leukemia cells. Blood 74, 1747-54 (1989).

44. Hennings, H., Blumberg, P.M., Petit, G.R., Herald, C.L., Shores, R.A., Yuspa, S.H. Bryostatin 1, an activator of protein kinase C, inhibits tumor promotion by phorbol esters in SENCAR mouse skin. Carcinogenesis 8, 1343-1346 (1987)

45. Kraft, A.S., Smith, J.B., Berkow, R.L. Bryostatin, an activator of the calcium phospholipid-dependent protein kinase, blocks phorbol ester-induced differentiation of human promyelocytic leukemia cells HL-60. Proc Natl Acad Sci USA 83, 1334-38 (1986)

46. Szallasi, Z., Smith, C.B., Pettit, G.R., Blumberg, P.M. Differential regulation of protein kinase C isozymes by bryostatin 1 and phorbol 12-myristate 13-acetate in NIH 3T3 fibroblasts. J. Biol. Chem 269, 2118-24 (1994)

47. Hocevar, B.A., Fields, A.P. Selective translocation of II-protein kinase C to the nucleus of human promyelocytic leukemia cells. J. Biol. Chem. 266, 28-33 (1991).

48. Isakov, N., Galron, D., Mustelin, T., Pettit, G.R., and Altman, A. Inhibition of phorbol ester-induced T cell proliferation by bryostatin 1 is associated with rapid degradation of protein kinase C. J. Immunol. 150, 1195-1204 (1993)

49. Lee, H-W., Smith, L., Pettit, G.R., Vinitsky, A., Smith, J.B. Ubiquitinization of protein kinase C- and degradation by the proteosome. J. Biol. Chem. 271, 20973-20976 (1996)

50. Kraft, A.S., Williams, F., Pettit, G.R., Lilly, M.B. Varied differentiation responses of human leukemias to bryostatin 1. Cancer Res 49, 1287-93 (1989)

51. Stone, R.M., Sariban, E., Pettit, G.R., Kufe, D.W. Bryostatin 1 activates protein kinase C and induces monocytic differentiation of HL-60 cells. Blood 72, 208-213 (1998)

52. Asiedu, C., Biggs, J., Lilly, M., Kraft, A.S. Inhibition of leukemic cell growth by the protein kinase C activator bryostatin 1 correlates with the dephosphorylation of cyclin-dependent kinase 2. Cancer Res 55, 3716-20 (1995).

53. Jones, R., Sharkis, S., Miller, C., Rowinsky, E., Burke, P., and May, W.S. Bryostatin 1, a unique biologic response modifier: antileukemic activity in vitro. Blood 75, 1319-1323 (1990)

54. Grant, S., Traylor, R., Bhalla, K., McCrady, C., Pettit, G.R. Effect of a combined exposure to ara-C, bryostatin 1, and rGM-CSF on the in vitro clonogenic growth of normal and leukemic human hematopoietic progenitor cells. Leukemia 5, 432-439 (1993)

55. May, W.S., Sharkis, S.S., Esa, A.H., Gebbia, V., Kraft, A.S., Pettit, G.R. & Sensenbrenner, L.L. Antineoplastic bryostatins are multipotent stimulators of human hematopoietic progenitor cells. Proc Natl Acad Sci(USA) 84, 8483-8487 (1987)

56. Li, F., Grant, S., Pettit, G.R., McCrady, C. Effect of pharmacologic manipulation of protein kinase C (PKC) on the proliferation and lineage specificity of progenitor cell-enriched normal human bone marrow cells (MY-10+) exposed to rGM-CSF and rIL-3. Blood 80, 2495-2502 (1992).

57. Sharkis, S.J., Jones, R.J., Bellis, M.L., Demetri, G.D., Griffin, J.D., Civin, C., May, W.S. The action of bryostatin 1 on normal human hematopoietic progenitors is mediated by accessory cell release of growth factors. Blood 76, 716-721 (1990)

58. Nara, N., Curtis, J.E., Senn, J.S., Pritchler, D.L., McCulloch, E.A. The sensitivity to cytosine arabinoside of the blast progenitors of acute myeloblastic leukemia. Blood 67, 762-769 (1986)

59. Curtis, J.E., Messner, H.A., Hasselhock, R., Elkahem, T.M., McCulloch, E.A. Contributions of host and disease-related attributes to the outcome of patients with acute myelocytic leukemia (AML). Blood 2, 253-259 (1984)

60. Huang, Y., Waxman, S. Enhanced apoptosis in leukemia cells following treatment with combination fluoropyrimdines and differentiation inducers. Mol. Cell. Differ. 2, 83-100 (1994.)

61. Studzinski, G.P., Reddy, K.B., Hill, H.Z., Bhandal, A.K. Potentiation of 1--D-arabinofuranosylcytosine cytotoxicity by 1,25-dihydroxyvitamin D₃ correlates with reduced rate of maturation of DNA replication intermediates. Cancer Res. 51, 3451-55 (1991)

62. Bhatia, U., Traganos, F., Darzynkiewicz, Z. Induction of cell differentiation potentiates apoptosis triggered by prior exposure to DNA-damaging drugs. Cell Growth Diff. 6, 937-44 (1995)

63. Waxman, S., Huang, Y., Scher, B.M., Scher, W. Combination cytotoxic-differentiation therapy of mouse erythroleukemia cells with 5-fluorouracil and hexamethylene bisacetamide. Cancer Res. 50, 3878-3887 (1990)

64. Grant, S., Jarvis, W.D., Turner, A.J., Wallace, H., Pettit, G.R. Effect of bryostatin 1 and rGM-CSF on the metabolism of 1--D-arabinofuranosylcytosine in human leukemic myeloblasts. British Journal of Haematology 82, 522-528 (1992)

65. Grant, S., McCrady, C., Boise, L., Westin, E., Pettit, G.R. Effects of bryostatin 1 on the metabolism and cytoxicity of 1--D-arabinofuranosylcytosine in human leukemia cells. Biochemical Pharmacol 42, 853-867 (1991)

66. Grant S, Jarvis D, Swerdlow P, Turner A, Traylor R, Wallace H, Lin, P-S, Pettit GR, Gewirtz DA: Potentiation of the activity of 1--D-arabinofuranosylcytosine by the macrocyclic lactone PKC activator bryostatin 1 is associated with enhanced fragmentation of mature DNA. Cancer Res 52, 6270-6278 (1992).

67. Jarvis WD, Gewirtz DA, Povirk L, Turner A, Traylor R, Pettit GR, Grant S: Effect of bryostatin 1 and other activators of protein kinase C on 1--D-arabinofuranosylcytosine-induced apoptosis in HL-60 human promyelocytic leukemia cells. Biochem Pharmacol 47, 839-852 (1994)

68. Forbes, I.J., Zalewski, P.D., Giannakis, C., Cowled, P.A. Induction of apoptosis in chronic lymphocytic leukemia cells and its prevention by phorbol ester. Exp. Cell Res. 198, 367-372 (1992)

69. Bertrand, R., Solary, E., O'Connor, P., Kohn, K.W., Pommier, Y. Induction of a common pathway of apoptosis by staurosporine. Exp Cell Res 211, 314-321 (1994)

70. Grant, S., Turner, A., Bartimole, T.M., Nelms, P., Joe, V.C., Jarvis, W.D. . Modulation of 1--D-arabinofuranosylcytosine-induced apoptosis in human promyelocytic leukemia cells by staurosporine and other inhibitors of protein kinase C. Oncology Research 6, 87-99 (1994)

71. Kyriakis, J.M., Banerjee, P., Nikolakaki, E., Dai, T., Rubin, E.A., Ahmand, M.F., Avruch, J., Woodgett, J.R. The stress-activated protein kinase subfamily of c-Jun kinases. Nature(Lond.) 369, 156-160 (1994)

72. Cano, E., Mahadevan, L.C. Parallel signal processing among mammalian mitogen-activated protein kinases. Trends Biol. Sci. 20, 117-122 (1996)

73. Cuvillier, O., Pirianov, G., Kleuser, B., Vanek, P.G., Coso, O.A., Gutkind, J.S., Spiegel, S. Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate. Nature 381, 800-803 (1996)

74. Xia, Z., Dickens, M., Raingeaud, J., David, R.J., Greenberg, M.E. Opposing effects of ERK, JNK, and RK kinases on apoptosis. Science 270, 1326-1331 (1995)

75. Martin, S.J., Bradley, J.G., Cotter, T.G. HL-60 cells differentiate towards neutrophils subsequently die via apoptosis. Clin Exp Immunol 79, 448-453 (1990)

76. Solary, E., Bertrand, R., Pommier, Y. Apoptosis of human leukemic HL-60 cells induced to differentiate by phorbol ester treatment. Leukemia 8, 792-797 (1994)

77. Solary, E., Bertrand, R., Kohn, K., Pommier, Y. Differential induction of apoptosis in undifferentiated and differentiated HL-60 cells by DNA topoisomerase I and II inhibitors. Blood 81, 1359-1368 (1993).

78. de Vente, J., Kiley, S., Garris, T., Bryant, W., Hooker, J., Posekany, K., Parker, P., Cook, P., Fletcher, D., Ways, D.K. Phorbol ester treatment of U937 cells with altered protein kinase C content and distribution induces cell death rather than differentiation. Cell Growth Diff. 6, 71-382 (1995)

79. Selvakumaran, M., Reed, J.C., Liebermann, D., Hoffman, B. Progression of the myeloid differentiation program is dominant to transforming growth factor- 1-induced apoptosis in M1 myeloid leukemia cells. Blood 84, 1036-1042 (1994)

80. Grant, S., Rao, A., Freemerman, A.J., Turner, A.J., Kornstein, M.J., Chelliah, J., Jarvis, W.D. Divergent effects of calcium ionophore (A23187) on bryostatin 1-related differentiation and apoptosis in human promyelocytic leukemia cells (HL-60). Mol. Cell Diff. 3, 337-359 (1995)

81. Rao, A.S., Freemerman, A.J., Jarvis, W.D., Chelliah, J., Bear, H.D., Mikkelsen, R., Grant, S. Effects of AS101 on bryostatin 1-mediated differentiation induction, cell cycle arrest, and modulation of drug-induced apoptosis in human myeloid leukemia cells. Leukemia 10, 1150-1158 (1996)

82. Huang, Y., Waxman, S. Enhanced apoptosis in leukemia cells following treatment with combination fluoropyrimidines and differentiation inducers. Mol Cell Diff 2, 83-100 (1994)

83. Studzinski, G.P., Reddy, K.B., Hill, H.Z., Bhandal, A.K. Potentiation of 1--D-arabinofuranosylcytosine cytotoxicity to HL-60 cells by 1,25-dihydroxyvitamin D3 correlates with reduced rate of maturation of DNA replication intermediates. Cancer Res 51, 3451-3455 (1991).

84. Bhatia, U., Traganos, F., Darzynkciewicz, Z. Induction of cell differentiation potentiates apoptosis triggered by prior exposure to DNA damaging drugs. Cell Growth Diff 6, 937-944 (1995)

85. Grant, S., Turner, A.J., Freemerman, A.J., Wang, Z., Kramer, L., Jarvis, W.D. Modulation of protein kinase C activity and calcium-sensitive isoform expression in human myeloid leukemia cells by bryostatin 1: relationship to differentiation and ara-C-induced apoptosis. Exp Cell Res 228, 65-75 (1996)

86. Kato G., Dang C.V. Function of the c-Myc oncoprotein. FASEB J 6, 3065-3072 (1992)

87. Galaktionov, K., Chen, X., Beach, D. Cdc25 cell-cycle phosphatase as a target of c-myc. Nature 382, 511-517 (1996)

88. Kraft AS, Baker VV, and May WS, Bryostatin 1 induces changes in protein kinase C location and activity without altering c-myc expression in human promyelocytic leukemia cells (HL-60). Oncogene 1, 111-118 (1987)

89. Askew DS, Ashmun RA, Simmons BC, and Cleveland JL, Constitutive c-myc expression in an IL-3-dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis. Oncogene 6, 1915-1922 (1991)

90. Chelliah, J., Freemerman, A.J., Wu-Pong, S., Jarvis, W.D., Grant, S. Potentiation of ara-C-induced apoptosis by the protein kinase C activator bryostatin 1 in human leukemia cells (HL-60) involves a process dependent upon c-Myc. Biochemical Pharmacol. In Press.

91. Reed, J.C. Bcl-2 and the regulators of programmed cell death. J. Cell Biol. 124, 1-6 (1994).

92. Yang, E., Korsmeyer, S.J. Molecular thanatopsis: a discourse on the BCL2 family and cell death. Blood 88, 386-401 (1996)

93. Oltavi, Z.N., Milliman, C.L., and Korsmeyer, S.J. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74, 609-619 (1993)

94. Chinnaiyan, A.M., Orth, K., O'Rourke, K., Duan, H., Poirer, G.G., Dixit, V.M. Molecular ordering of the cell death pathway: bcl-2 and bcl-xL function upstream of the CED-3-like apoptotic proteases. J. Biol. Chem. 271, 4573-4576 (1996)

95. Tewari, M., Quan, L.T., O'Rourke, K., Desnoyers, S., Zeng, Z., Beidler, D.R., Poirer, G.G., Salvesan, G.S., Dixit, V.M. Yama/CPP32 , a mammalian homolog of CED-3, is a Crm-inibitable protease that cleaves the death substrate poly(ADP-ribose)polymerase. J. Biol. Chem. 267, 30761-30764 (1994)

96. Ibrado, A.M., Huang, Y., Fang, G., Liu, L., Bhalla, K. Overexpression of Bcl-2 or Bcl-xL inhibits ara-C-induced CPP32/Yama protease activity and apoptosis of human acute myelogenous leukemia HL-60 cells. Cancer Res. 56, 4743-4748 (1996)

97. Liu, X., Kim, C.N., Yang, J., Jemmerson, R., Wang, X. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86, 147-157 (1996)

98. Yang, J., Liu, X., Bhalla, K., Kim, C.N., Ibrado, A.M., Cai, J., Peng, T-I, Jones, D.P., Wang, X. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 275, 1129-1132 (1997)

99. Minn, A.J., Velez, P., Schendel, S.L., Liang, H., Muchmore, S.W., Fesik, S.W., Fill, M., Thompson, C.B. Bcl-xL forms an ion channel in synthetic lipid membranes. Nature 385, 353-357 (1997)

100. Delia, D., Aiello, A., Soligo, D., Fontanella, E., Melani, C., Pezzela, F., Pierotti, M.A. Della Porta, G. Bcl2 proto-oncogene expression in normal and neoplastic human myeloid cells. Blood 79, 1291-1297 (1992)

101. Hu, Z-B., Minden, M.D., McCulloch, E.A. Direct evidence for the participation of bcl-2 in the regulation by retinoic acid of the ara-C sensitivity of leukemic stem cells. Leukemia 9, 1667-1673 (1995)

102. Lotem, J., Sachs, L. Regulation of bcl-2, bcl-xL, and bax in the control of apoptosis by hematopoietic cytokines and dexamethasone. Cell Growth Diff. 6, 647-653 (1995)

103. Maki, A., Diwkaran, H., Redman, B., Al-Asfar, S., Pettit, G.R., Mohammad, R.M., Al-Katib, A. The bcl-2 and p53 oncoproteins can be modulated by bryostatin 1 and dolostatins in human large cell lymphoma. Anti-Cancer Drugs 6, 392-397 (1995)

104. Bartimole, T.M., Vrana, J.A., Freemerman, A.J., Jarvis, W.D. Reed, J.C., Boise, L.H., Grant, S. Modulation of the expression of Bcl-2 and related proteins in human leukemia cells by protein kinase C activators: relationship to effects on 1--D-arabinofuranosylcytosine-induced apoptosis. Cell Death Diff 4, 294-303 (1997)

105. Gajewski, T.F., Thompson, C.B. Apoptosis meets signal transduction: elimination of a BAD influence. Cell 87, 589-592 (1996)

106. Haldar, S., Jena, N., Croce, C.M. Inactivation of Bcl-2 by phosphorylation. Proc. Natl. Acad. Sci. (USA) 92, 4352-4356 (1995)

107. Blagsklonny, M.V., Giannakakou, P., El-Diery, W.S., Kingston, D.G.I., Higgs, P.I.,Neckers, L., Fojo, T. Raf1/bcl-2 phosphorylation: a step from microtubule damage to cell death. Cancer Res. 57, 130-135 (1997)

108. Haldar, S., Chintapalli, J., Croce, C.M. Taxol induces bcl-2 phosphorylation and death of prostate cancer cells. Cancer Res. 56, 1253-1255 (1996)

109. May, W.S., Tyler, G., Ito, T., Armstrong, D.K., Qatsha, K.A., Davidson, N.E. Interleukin-3 and bryostatin 1 mediate hyperphosphorylation of BCL2 in association with suppression of apoptosis. J. Biol. Chem 269, 26865-26870 (1994)

110. Grant, S., Wang, S., Vrana, J., Bartimole, T., Krystal, G., Jarvis, W.D., Dent, P. Reversal of Bcl-2-mediated resistance to ara-C-mediated apoptosis in human myeloid leukemia cells by down-regulation or inhibition of protein kinase C. Proc. Am. Assoc. Cancer Res. 38, 620 (1997)

111. Schwartz, G.K., Haimovitz-Friedman, A., Dhupar, S.K., Ehlieter, D., Maslak, P., Lai, L., Loganzo, F., Kelsen, D.P. Potentiation of apoptosis by treatment with the protein kinase C-specific inhibitor safingol in mitomycin C-treated gastric cancer cells. J. Natl. Cancer Inst. 87, 1394-1399 (1995)