Apoptosis induction by the dual-action DNA- and protein-reactive antitumor drug irofulven is largely Bcl-2-independent

Biochemical Pharmacology

Volumn 65, Issue 4, 2003, Pages 503-513

  Herzig, Maryanne C S ^a   Trevino, Alex V ^a   Liang, Huiyun ^a   Salinas, Richard ^a   Waters, Stephen J ^b   MacDonald, John R ^b   Woynarowska, Barbara A ^a   Woynarowski, Jan M ^a  

^a UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

^b GUILFORD PHARMACEUTICALS INC   (United States)

Author keywords

Apoptosis; Bcl 2 overexpression; Helenalin A; Irofulven; Mitochondria; Protein damage

Indexed keywords

6 HYDROXYMETHYLACYLFULVENE; ANTINEOPLASTIC AGENT; CASPASE; CASPASE INHIBITOR; DNA; DNA FRAGMENT; DNA TOPOISOMERASE (ATP HYDROLYSING); ETOPOSIDE; HELENALIN; IROFULVEN; PHOSPHATIDYLCHOLINE; PROTEIN; PROTEIN BCL 2; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CELL GROWTH; CONTROLLED STUDY; DNA DAMAGE; DRUG DNA INTERACTION; DRUG MECHANISM; DRUG PROTEIN BINDING; GENE OVEREXPRESSION; HELA CELL; HUMAN; HUMAN CELL; MEMBRANE POTENTIAL; MITOCHONDRIAL MEMBRANE; PRIORITY JOURNAL; PROTEIN FUNCTION; SIGNAL TRANSDUCTION;

ANTINEOPLASTIC AGENTS; APOPTOSIS; DNA FRAGMENTATION; GENE EXPRESSION REGULATION; HELA CELLS; HUMANS; PROTO-ONCOGENE PROTEINS C-BCL-2; SESQUITERPENES;

EID: 0037441340     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0006-2952(02)01552-6     Document Type: Article

References (87)

1. Blalock W.L., Weinstein-Oppenheimer C., Chang F., Hoyle P.E., Wang X.Y., Algate P.A., Franklin R.A., Oberhaus S.M., Steelman L.S., McCubrey J.A. Signal transduction, cell cycle regulatory, and anti-apoptotic pathways regulated by IL-3 in hematopoietic cells: possible sites for intervention with anti-neoplastic drugs. Leukemia. 13:1999;1109-1166.
2. Kaufmann S.H., Earnshaw W.C. Induction of apoptosis by cancer chemotherapy. Exp. Cell Res. 256:2000;42-49.
3. Glinsky G.V., Glinsky V.V., Ivanova A.B., Hueser C.J. Apoptosis and metastasis: increased apoptosis resistance of metastatic cancer cells is associated with the profound deficiency of apoptosis execution mechanisms. Cancer Lett. 115:1997;185-193.
4. Susin S.A., Zamzami N., Kroemer G. Mitochondria as regulators of apoptosis: doubt no more. Biochim. Biophys. Acta. 1366:1998;151-165.
5. Desagher S., Martinou J.C. Mitochondria as the central control point of apoptosis. Trends Cell Biol. 10:2000;369-377.
6. Zamzami N., Brenner C., Marzo I., Susin S.A., Kroemer G. Subcellular and submitochondrial mode of action of Bcl-2-like oncoproteins. Oncogene. 16:1998;2265-2282.
7. Korsmeyer S.J. BCL-2 gene family and the regulation of programmed cell death. Cancer Res. 59:1999;1693s-1700s.
8. Bae J., Hsu S.Y., Leo C.P., Zell K., Hsueh A.J. Underphosphorylated BAD interacts with diverse anti-apoptotic Bcl-2 family proteins to regulate apoptosis. Apoptosis. 6:2001;319-330.
9. Hsu S.Y., Kaipia A., McGee E., Lomeli M., Hsueh A.J. Bok is a pro-apoptotic Bcl-2 protein with restricted expression in reproductive tissues and heterodimerizes with selective anti-apoptotic Bcl-2 family members. Proc. Natl. Acad. Sci. U.S.A. 94:1997;12401-12406.
10. Tsujimoto Y., Shimizu S. Bcl-2 family: life-or-death switch. FEBS Lett. 466:2000;6-10.
11. Kusenda J. Bcl-2 family proteins and leukemia. Neoplasma. 45:1998;117-122.
12. Halestrap A.P., Doran E., Gillespie J.P., O'Toole A. Mitochondria and cell death. Biochem. Soc. Trans. 28:2000;170-177.
13. Loeffler M., Kroemer G. The mitochondrion in cell death control: certainties and incognita. Exp. Cell Res. 256:2000;19-26.
14. Nuessler V., Stötzer O., Gullis E., Pelka-Fleischer R., Pogrebniak A., Gieseler F., Wilmanns W. Bcl-2, bax and bcl-xL expression in human sensitive and resistant leukemia cell lines. Leukemia. 13:1999;1864-1872.
15. Planchon S.M., Wuerzberger-Davis S.M., Pink J.J., Robertson K.A., Bornmann W.G., Boothman D.A. Bcl-2 protects against beta-lapachone-mediated caspase 3 activation and apoptosis in human myeloid leukemia (HL-60) cells. Oncol. Rep. 6:1999;485-492.
16. Takahashi M., Saito H., Okuyama T., Miyashita T., Kosuga M., Sumisa F., Yamada M., Ebinuma H., Ishii H. Overexpression of Bcl-2 protects human hepatoma cells from Fas-antibody-mediated apoptosis. J. Hepatol. 31:1999;315-322.
17. Bloem A., Lockhorst H. Bcl-2 antisense therapy in multiple myeloma. Pathol. Biol. 47:1999;216-220.
18. Chaudhary K.S., Abel P.D., Lalani E.N. Role of the Bcl-2 gene family in prostate cancer progression and its implications for therapeutic intervention. Environ Health Perspect. 107(Suppl. 1):1999;49-57.
19. McConkey D.J., Greene G., Pettaway C.A. Apoptosis resistance increases with metastatic potential in cells of the human LNCaP prostate carcinoma line. Cancer Res. 56:1996;5594-5599.
20. Krajewska M., Krajewski S., Epstein J.I., Shabaik A., Sauvageot J., Song K., Kitada S., Reed J.C. Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers. Am. J. Pathol. 148:1996;1567-1576.
21. DiPaola R.S., Aisner J. Overcoming bcl-2- and p53-mediated resistance in prostate cancer. Semin. Oncol. 26(Suppl. 1):1999;112-116.
22. Pepper C., Bentley P., Hoy T. Regulation of clinical chemoresistance by bcl-2 and bax oncoproteins in B-cell chronic lymphocytic leukaemia. Br. J. Haematol. 95:1996;513-517.
23. Lopes de Menezes D.E., Hudon N., McIntosh N., Mayer L.D. Molecular and pharmacokinetic properties associated with the therapeutics of bcl-2 antisense oligonucleotide G3139 combined with free and liposomal doxorubicin. Clin. Cancer Res. 6:2000;2891-2902.
24. Huang H., Cheville J.C., Pan Y., Roche P.C., Schmidt L.J., Tindall D.J. PTEN induces chemosensitivity in PTEN-mutated prostate cancer cells by suppression of bcl-2 expression. J. Biol. Chem. 276:2001;38830-38836.
25. Krajewski S., Krajewska M., Turner B.C., Pratt C., Howard B., Zapata J.M., Frenkel V., Robertson S., Ionov Y., Yamamoto H., Perucho M., Takayama S., Reed J.C. Prognostic significance of apoptosis regulators in breast cancer. Endocr. Relat. Cancer. 6:1999;29-40.
26. Borner C., Schlagbauer Wadl H., Fellay I., Selzer E., Polterauer P., Jansen B. Mutated N-ras upregulates Bcl-2 in human melanoma in vitro and in SCID mice. Melanoma Res. 9:1999;347-350.
27. Reed J.C. Bcl-2 family proteins. Oncogene. 17:1998;3225-3236.
28. Koukourakis M.I., Corti L., Skarlatos J., Giatromanolaki A., Krammer B., Blandamura S., Piazza M., Verwanger T., Schnitzhofer G., Kostandelos J., Beroukas K. Clinical and experimental evidence of Bcl-2 involvement in the response to photodynamic therapy. Anticancer Res. 21:2001;663-668.
29. Huang C.-I., Kohno N., Inufusa H., Kodama K., Taki T., Miyake M. Overexpression of bax associated with mutations in the loop-sheet-helix motif of p53. Am. J. Pathol. 155:1999;955-965.
30. Stoetzer O.J., Pogrebniak A., Scholz M., Pelka-Fleischer R., Gullis E., Darsow M., Nussler V., Wilmanns W. Drug-induced apoptosis in chronic lymphocytic leukemia. Leukemia. 13:1999;1873-1880.
31. Eckhardt S.G., Baker S.D., Britten C.D., Hidalgo M., Siu L., Hammond L.A., Villalona-Calero M.A., Felton S., Drengler R., Kuhn J.G., Clark G.M., Smith S.L., MacDonald J.R., Smith C., Moczygemba J., Weitman S., Von Hoff D.D., Rowinsky E.K. Phase I and pharmacokinetic study of irofulven, a novel mushroom-derived cytotoxin, administered for five consecutive days every four weeks in patients with advanced solid malignancies. J. Clin. Oncol. 18:2000;4086-4097.
32. Kelner M.J., McMorris T.C., Estes L., Wang W., Samson K.M., Taetle R. Efficacy of HMAF (MGI-114) in the MV522 metastatic lung carcinoma xenograft model non-responsive to traditional anticancer agents. Invest New Drugs. 14:1996;161-167.
33. MacDonald J.R., Muscoplat C.C., Dexter D.L., Mangold G.L., Chen S.F., Kelner M.J., McMorris T.C., Von Hoff D.D. Preclinical antitumor activity of 6-hydroxymethylacylfulvene, a semisynthetic derivative of the mushroom toxin illudin S. Cancer Res. 57:1997;279-283.
34. Hidalgo M., Izbicka E., Eckhardt S.G., MacDonald J.R., Cerna C., Gomez L., Rowinsky E.K., Weitman S.D., Von Hoff D.D. Antitumor activity of MGI 114 (6-hydroxymethylacylfulvene, HMAF), a semisynthetic derivative of illudin S, against adult and pediatric human tumor colony-forming units. Anticancer Drugs. 10:1999;837-844.
35. Weitman S., Barrera H., Moore R., Gonzalez C., Marty J., Hilsenbeck S., MacDonald J.R., Waters S.J., Von Hoff D. MGI 114: augmentation of antitumor activity when combined with topotecan. J. Pediatr. Hematol. Oncol. 22:2000;306-314.
36. Sato Y., Kashimoto S., MacDonald J.R., Nakano K. In vivo antitumour efficacy of MGI-114 (6-hydroxymethylacylfulvene, HMAF) in various human tumour xenograft models including several lung and gastric tumours. Eur. J. Cancer. 37:2001;1419-1428.
37. Woynarowski J.M., Napier C., Koester S.K., Chen S.F., Troyer D., Chapman W., MacDonald J.R. Effects on DNA integrity and apoptosis induction by a novel antitumor sesquiterpene drug, 6-hydroxymethylacylfulvene (HMAF, MGI 114). Biochem. Pharmacol. 54:1997;1181-1193.
38. Herzig M.C.S., Arnett B., MacDonald J.R., Woynarowski J.M. Drug uptake and cellular targets of hydroxymethylacylfulvene (HMAF). Biochem. Pharmacol. 58:1999;217-225.
39. Woynarowska B.A., Roberts K., Woynarowski J.M., MacDonald J.R., Herman T.S. Targeting apoptosis by hydroxymethylacylfulvene in combination with gamma radiation in prostate tumor cells. Radiat. Res. 154:2000;429-438.
40. Woynarowska B.A., Woynarowski J.M., Herzig M.C.S., Roberts K., Higdon A.L., MacDonald J.R. Differential cytotoxicity and induction of apoptosis in tumor and normal cells by hydroxymethylacylfulvene (HMAF). Biochem. Pharmacol. 59:2000;1217-1226.
41. McMorris T.C., Elayadi A.N., Yu J., Hu Y., Kelner M.J. Metabolism of antitumor hydroxymethylacylfulvene by rat liver cytosol. Drug Metab. Dispos. 27:1999;983-985.
42. Kamesaki S., Kamesaki H., Jorgensen T.J., Tanizawa A., Pommier Y., Cossman J. Bcl-2 protein inhibits etoposide-induced apoptosis through its effects on events subsequent to topoisomerase II-induced DNA strand breaks and their repair. Cancer Res. 53:1993;4251-4256.
43. Granville D.J., Jiang H., An M.T., Levy J.G., McManus B.M., Hunt D.W. Bcl-2 overexpression blocks caspase activation and downstream apoptotic events instigated by photodynamic therapy. Br. J. Cancer. 79:1999;95-100.
44. L inhibits Ara-C-induced CPP32/Yama protease activity and apoptosis of human acute myelogenous leukemia HL-60 cells. Cancer Res. 56:1996;4743-4748.
45. Walton M.I., Whysong D., O'Connor P.M., Hockenbery D., Korsmeyer S.J., Kohn K.W. Constitutive expression of human Bcl-2 modulates nitrogen mustard and camptothecin induced apoptosis. Cancer Res. 53:1993;1853-1861.
46. Marchetti P., Decaudin D., Macho A., Zamzami N., Hirsch T., Susin S.A., Kroemer G. Redox regulation of apoptosis: impact of thiol oxidation status on mitochondrial function. Eur. J. Immunol. 27:1997;289-296.
47. Mirkovic N., Voehringer D.W., Story M.D., McConkey D.J., McDonnell T.J., Meyn R.E. Resistance to radiation-induced apoptosis in Bcl-2-expressing cells is reversed by depleting cellular thiols. Oncogene. 15:1997;1461-1470.
48. Zamzami N., Marzo I., Susin S.A., Brenner C., Larochette N., Marchetti P., Reed J., Kofler R., Kroemer G. The thiol crosslinking agent diamide overcomes the apoptosis-inhibitory effect of Bcl-2 by enforcing mitochondrial permeability transition. Oncogene. 16:1998;1055-1063.
49. Watson R.W., Rotstein O.D., Nathens A.B., Dackiw A.P., Marshall J.C. Thiol-mediated redox regulation of neutrophil apoptosis. Surgery. 120:1996;150-157. ; discussion 7-8.
50. Sato N., Iwata S., Nakamura K., Hori T., Mori K., Yodoi J. Thiol-mediated redox regulation of apoptosis. Possible roles of cellular thiols other than glutathione in T cell apoptosis. J. Immunol. 154:1995;3194-3203.
51. Coffey R.N., Watson R.W., Hegarty N.J., O'Neill A., Gibbons N., Brady H.R., Fitzpatrick J.M. Thiol-mediated apoptosis in prostate carcinoma cells. Cancer. 88:2000;2092-2104.
52. Costantini P., Belzacq A.S., Vieira H.L., Larochette N., de Pablo M.A., Zamzami N., Susin S.A., Brenner C., Kroemer G. Oxidation of a critical thiol residue of the adenine nucleotide translocator enforces Bcl-2-independent permeability transition pore opening and apoptosis. Oncogene. 19:2000;307-314.
53. Halestrap A.P., Woodfield K.Y., Connern C.P. Oxidative stress, thiol reagents, and membrane potential modulate the mitochondrial permeability transition by affecting nucleotide binding to the adenine nucleotide translocase. J. Biol. Chem. 272:1997;3346-3354.
54. Ueda S., Nakamura H., Masutani H., Sasada T., Yonehara S., Takabayashi A., Yamaoka Y., Yodoi J. Redox regulation of caspase-3(-like) protease activity: regulatory roles of thioredoxin and cytochrome c. J. Immunol. 161:1998;6689-6695.
55. L or Bcl-2. Cancer Res. 61:2001;5817-5823.
56. Woynarowska B.A., Woynarowski J.M. Preferential targeting of apoptosis in tumor versus normal cells. Biochim. Biophys. Acta. 1587:2002;309-317.
57. Yin D.X., Schimke R.T. BCL-2 expression delays drug-induced apoptosis but does not increase clonogenic survival after drug treatment in HeLa cells. Cancer Res. 55:1995;4922-4928.
58. Herzig M.C.S., Liang H., Johnson A.E., Woynarowska B., Woynarowski J.M. Irofulven induces apoptosis in breast cancer cells regardless of caspase-3 status. Breast Cancer Res. Treat. 71:2002;133-143.
59. Liang H, Herzig MCS, Salinas R, Weintraub S, Moyer MP, Waters SJ, Woynarowski JM, Woynarowska B. Pro-oxidative distortion of the cellular redox-homeostasis in irofulven-induced apoptosis. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, October 29-November 2, Miami, FL; 2001. p. 143.
60. Yin D.X., Zhu L., Schimke R.T. Tetracycline-controlled gene expression system achieves high-level and quantitative control of gene expression. Anal. Biochem. 235:1996;195-201.
61. Garner D.L., Thomas C.A., Joerg H.W., DeJarnette J.M., Marshall C.E. Fluorometric assessments of mitochondrial function and viability in cryopreserved bovine spermatozoa. Biol. Reprod. 57:1997;1401-1406.
62. 6(3) or rhodamine 123, is a reliable fluorescent probe to assess ΔΨ changes in intact cells: implications for studies on mitochondrial functionality during apoptosis. FEBS Lett. 411:1997;77-82.
63. Bedner E., Li X., Gorczyca W., Melamed M.R., Darzynkiewicz Z. Analysis of apoptosis by laser scanning cytometry. Cytometry. 35:1999;181-195.
64. Vermes I., Haanen C., Reutelingsperger C. Flow cytometry of apoptotic cell death. J. Immunol. Methods. 243:2000;167-190.
65. Koester S.K., Bolton W.E. Differentiation and assessment of cell death. Clin. Chem. Lab. Med. 37:1999;311-317.
66. O'Brien M.C., Healy S.F. Jr., Raney S.R., Hurst J.M., Avner B., Hanly A., Mies C., Freeman J.W., Snow C., Koester S.K., Bolton W.E. Discrimination of late apoptotic/necrotic cells (type III) by flow cytometry in solid tumors. Cytometry. 28:1997;81-89.
67. Williams W.L. Jr., Hall I.H., Grippo A.A., Oswald C.B., Lee K.H., Holbrook D.J., Chaney S.G. Inhibition of nucleic acid synthesis in P-388 lymphocytic leukemia tumor cells by helenalin and bis(helenalinyl)malonate in vivo. J. Pharm. Sci. 77:1988;178-184.
68. Lock R.B., Stribinskiene L. Dual modes of death induced by etoposide in human epithelial tumor cells allow Bcl-2 to inhibit apoptosis without affecting clonogenic survival. Cancer Res. 56:1996;4006-4012.
69. Tsujimoto Y. Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria? Genes Cells. 3:1998;697-707.
70. Shimizu S., Narita M., Tsujimoto Y. Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC [see comments]. Nature. 399:1999;483-487.
71. Harris M.H., Thompson C.B. The role of the Bcl-2 family in the regulation of outer mitochondrial membrane permeability. Cell Death Differ. 7:2000;1182-1191.
72. Gao G., Dou Q.P. N-terminal cleavage of Bax by calpain generates a potent pro-apoptotic 18-kDa fragment that promotes Bcl-2-independent cytochrome c release and apoptotic cell death. J. Cell Biochem. 80:2000;53-72.
73. Liang H., Munoz R., Hidgon A.L., Waters S.J., Woynarowska B. Early events in apoptosis induced by irofulven (hydroxymethylacylfulvene) in prostate tumor cells. Proc. Am. Assoc. Cancer Res. 42:2001;640.
74. Chen M.-C., Hsu T.-L., Luh T.-Y., Hsieh S.-L. Overexpression of Bcl-2 enhances LIGHT- and interferon-γ-mediated apoptosis in Hep3BT2 cells. J. Biol. Chem. 275:2000;38794-38801.
75. Chen Q., Gong B., Almasan A. Distinct stages of cytochrome c release from mitochondria: evidence for a feedback amplification loop linking caspase activation to mitochondrial dysfunction in genotoxic stress induced apoptosis. Cell Death Differ. 7:2000;227-233.
76. Kirsch D.G., Doseff A., Chau B.N., Lim D.-S., de Souza-Pinto N.C., Hansford R., Kastan M.B., Lazebnik Y.A., Hardwick J.M. Caspase-3-dependent cleavage of Bcl-2 promotes release of cytochrome c. J. Biol. Chem. 274:1999;21155-21161.
77. Zamzami N., El Hamel C., Maisse C., Brenner C., Munoz-Pinedo C., Belzacq A.-S., Costantini P., Vieira H., Loeffler M., Molle G., Kroemer G. Bid acts on the permeability transition pore complex to induce apoptosis. Oncogene. 19:2000;6342-6350.
78. Lee K.-H., Hall I.H., Mar E.-C., Starnes C.O., ElGebaly S.A., Waddell T.G., Hadgraft R.I., Ruffner C.G., Weidner I. Sesquiterpene antitumor agents: inhibitors of cellular metabolism. Science. 196:1977;533-536.
79. Frommel T.O., Zarling E.J. Chronic inflammation and cancer: potential role of Bcl-2 gene family members as regulators of cellular antioxidant status. Med. Hypotheses. 52:1999;27-30.
80. Lee M., Hyun D.H., Marshall K.A., Ellerby L.M., Bredesen D.E., Jenner P., Halliwell B. Effect of overexpression of Bcl-2 on cellular oxidative damage, nitric oxide production, antioxidant defenses, and the proteasome. Free Radic. Biol. Med. 31:2001;1550-1559.
81. Voehringer D.W., Meyn R.E. Redox aspects of Bcl-2 function. Antioxid. Redox. Signal. 2:2000;537-550.
82. Holmgren A. Antioxidant function of thioredoxin and glutaredoxin systems. Antioxid. Redox. Signal. 2:2000;811-820.
83. Powis G., Mustacich D., Coon A. The role of the redox protein thioredoxin in cell growth and cancer. Free Radic. Biol. Med. 29:2000;312-322.
84. Nordberg J., Arner E.S. Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic. Biol. Med. 31:2001;1287-1312.
85. Chaudhary K.S., Abel P.D., Stamp G.W.H., Lalani E. Differential expression of cell death regulators in response to thapsigargin and adriamycin in Bcl-2 transfected DU145 prostatic cancer cells. J. Pathol. 193:2001;522-529.
86. Del Bufalo D., Trisciuoglio D., Biroccio A., Marcocci L., Buglioni S., Candiloro A., Scarsella M., Leonetti C., Zupi G. Bcl-2 overexpression decreases BCNU sensitivity of a human glioblastoma line through enhancement of catalase activity. J. Cell Biochem. 83:2001;473-483.
87. Biroccio A., Candiloro A., Mottolese M., Sapora O., Albini A., Zupi G., Del Bufalo D. Bcl-2 overexpression and hypoxia synergistically act to modulate vascular endothelial growth factor expression and in vivo angiogenesis in a breast carcinoma line. FASEB J. 14:2000;652-660.