Combined targeted inhibition of bcl-2, bcl-XL, epidermal growth factor receptor, and protein kinase A type I causes potent antitumor, apoptotic, and antiangiogenic activity

Clinical Cancer Research

Volumn 9, Issue 2, 2003, Pages 866-871

  Tortora, Giampaolo ^a   Caputo, Rosa ^a   Damiano, Vincenzo ^a   Caputo, Roberta ^a   Troiani, Teresa ^a   Veneziani, Bianca Maria ^a   De Placido, Sabino ^a   Bianco, Angelo Raffaele ^a   Zangemeister Wittke, Uwe ^b   Ciardiello, Fortunato ^a  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^b UNIVERSITY HOSPITAL ZURICH   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; ANTISENSE OLIGONUCLEOTIDE; COMPOUND 4625; CYCLIC AMP DEPENDENT PROTEIN KINASE; EPIDERMAL GROWTH FACTOR RECEPTOR; GEFITINIB; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN KINASE AI ANTISENSE OLIGONUCLEOTIDE; UNCLASSIFIED DRUG; VASCULOTROPIN;

ANGIOGENESIS; APOPTOSIS; ARTICLE; CONTROLLED STUDY; GROWTH INHIBITION; HUMAN; HUMAN CELL; IN VITRO STUDY; INHIBITION KINETICS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; PROTEIN SYNTHESIS;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; BCL-X PROTEIN; BREAST NEOPLASMS; CELL DEATH; CELL DIVISION; COLONIC NEOPLASMS; CYCLIC AMP-DEPENDENT PROTEIN KINASES; ENDOTHELIAL GROWTH FACTORS; FEMALE; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; LYMPHOKINES; MICE; MICE, NUDE; NEOVASCULARIZATION, PATHOLOGIC; OLIGONUCLEOTIDES, ANTISENSE; PROTO-ONCOGENE PROTEINS C-BCL-2; QUINAZOLINES; RECEPTOR, EPIDERMAL GROWTH FACTOR; TRANSFECTION; TRANSPLANTATION, HETEROLOGOUS; TUMOR CELLS, CULTURED; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTORS;

EID: 0037312522     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (35)

1. Reed, J. Dysregulation of apoptosis in cancer. J. Clin. Oncol., 17: 2941-2953, 1999.
2. Sellers, W. R., and Fisher, D. E. Apoptosis and cancer drug targeting. J. Clin. Investig., 104: 1655-1661, 1999.
3. Jansen, B., Wacheck, V., Heere-Ress, E., Schlagbauer-Wadl, H., Hoeller, C., Lucas, T., Hoermann, M., Hollenstein, U., Wolff, K., and Pehamberger, H. A. Chemosensitisation of malignant melanoma by BCL2 antisense therapy. Lancet, 356: 1728-1733, 2000.
4. Waters, J. S., Webb, A., Cunningham, D., Clarke, P., F., Raynaud, di Stefano, F., and Cotter, F. E. Phase I clinical and pharmacokinetic study of bcl-2 antisense oligonucleotide therapy in patients with non Hodgkin's lymphoma. J. Clin. Oncol., 18: 1812-1823, 2000.
5. Boise, L-H., González-Garcia, M., Postema, C. E., Ding, L., Lindstein, T., Turka, L. A., Mao, X., Nunez, G., and Thompson, C. B. bcl-x, a bcl-2 related gene that functions as a dominant regulator of apoptotic cell death. Cell, 74: 597-608, 1993.
6. Simonian, P. L., Grillot, D. A., and Nunez, G. Bcl-2 and Bcl-xL can differentially block chemotherapy-induced cell death. Blood, 90: 1208-1216, 1997.
7. Zangemeister-Wittke, U., Leech, S. H., Olie, R. A., Simoes-Wust, A. P., Gautschi, O., Luedke, G. H., Natt, F., Nalin, C. M., and Stahel, R. A. A novel bispecific antisense oligonucleotide inhibiting both bcl-2 and bcl-xL expression efficiently induces apoptosis in tumor cells. Clin. Cancer Res., 6: 2547-2555, 2000.
8. Gautschi, O., Tschopp, S., Olie, R. A., Leech, S. H., Simoes-Wust, A. P., Ziegler, A., Baumann, B., Odermatt, B., Hall, J., Stahel, R. A., and Zangemeister-Wittke, U. Activity of a novel bcl-2/bcl-xL-bispecific antisense oligonucleotide against tumors of diverse histologic origins. J. Natl. Cancer Inst. (Bethesda), 93: 463-471, 2001.
9. Cho-Chung, Y. S., Pepe, S., Clair, T., Budillon, A., and Nesterova, M. cAMP-dependent protein kinase: role in normal and malignant growth. Crit. Rev. Oncol. Hematol., 21: 33-61, 1995.
10. Tortora, G., and Ciardiello, F. Targeting of epidermal growth factor receptor and protein kinase A: molecular basis and therapeutic applications. Ann. Oncol., 11: 777-783, 2000.
11. Tortora, G., Damiano, V., Bianco, C., Baldassarre, G., Bianco, A. R., Lanfrancone, L., Pelicci, P. G., and Ciardiello, F. The RIα subunit of protein kinase A (PKA) binds to Grb2 and allows PKA interaction with the activated EGF-receptor. Oncogene, 14: 923-928, 1997.
12. Ciardiello, F., Pepe, S., Bianco, C., Baldassarre, G., Ruggiero, A., Bianco, C., Selvam, M. P., Bianco, A. R., and Tortora, G. Downregulation of RIα subunit of the cAMP-dependent protein kinase induces growth inhibition of human mammary epithelial cells transformed by c-Ha-ras and c-erbB2 protooncogenes. Int. J. Cancer, 53: 438-443, 1997.
13. Nesterova, M., and Cho Chung, Y. S. A single-injection protein kinase A-directed antisense treatment to inhibit tumour growth. Nat. Med., 1: 528-533, 1997.
14. Tortora, G., Caputo, R., Damiano, V., Bianco, R., Pepe, S., Bianco, A. R., Jiang, Z., Agrawal, S., and Ciardiello, F. Synergistic inhibition of human cancer cell growth by cytotoxic drugs and mixed backbone antisense oligonucleotide targeting protein kinase A. Proc. Natl. Acad. Sci. USA, 94: 12586-12591, 1997.
15. Tortora, G., Bianco, R., Damiano, V., Fontanini, G., De Placido, S., Bianco, A. R., and Ciardiello, F. Oral antisense targeting protein kinase A cooperates with taxol and inhibits tumor growth, angiogenesis and growth factors production. Clin. Cancer Res., 6: 2506-2512, 2000.
16. Wang, H., Cai, Q., Zeng, X., Yu, D., Agrawal, S., and Zhang, R. Antitumor activity and pharmacokinetics of a mixed-backbone oligonucleotide targeted to the RIα subunit of protein kinase A following oral administration. Proc. Natl. Acad. Sci. USA, 96: 13989-13994, 1999.
17. Itano, Y., Ito, A., Uehara, T., and Nomura, Y. Regulation of bc-2 protein expression in human neuroblastoma SH-Sy5Y cells: positive and negative effects of protein kinase C and A respectively. J. Neurochem., 67: 131-137, 1996.
18. Srivastava, R. K., Srivastava, A. R., Korsmeyer, S. J., Nesterova, M., Cho-Chung, Y. S., and Longo, D. L. Involvement of microtubules in the regulation of Bcl2 phosphorylation and apoptosis through cAMP-dependent protein kinase. Mol. Cell. Biol., 18: 3509-3517, 1998.
19. Yang, W. L., Iacono, L., Tang, W. M., and Chin, K. V. Novel function of the regulatory subunit of protein kinase A: regulation of cytochrome c oxidase activity and release of cytochrome c release. Biochemistry, 37: 14175-14180, 1998.
20. Srivastava, R. K., Srivastava, A. R., Seth, P., Agrawal, S., and Cho-Chung, Y. S. Growth arrest and induction of apoptosis in breast cancer cells by antisense depletion of protein kinase A-RI alpha subunit: p53-independent mechanism of action. Mol. Cell Biochem., 18: 3509-3517, 1999.
21. Cho, Y. S., Kim, M. K., Tan, L., Srivastava, R., Agrawal, S., and Cho-Chung, Y. S. Protein kinase A RIα antisense inhibition of PC3M prostate cancer cell growth: Bcl-2 hyperphosphorylation, Bax upregulation and Bad hypophosphorylation. Clin. Cancer Res., 8: 607-614, 2002.
22. Mendelsohn, J., and Baselga, J. The EGF receptor family as targets for cancer therapy. Oncogene, 19: 6550-6565, 2000.
23. Woodburn, J. R. The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol. Ther., 82: 241-250, 1999.
24. Ciardiello, F., and Tortora, G. A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor. Clin. Cancer Res., 7: 2958-2970, 2001.
25. Ciardiello, F., Caputo, R., Bianco, R., Damiano, V., Pomatico, G., De Placido, S., Bianco, A. R., and Tortora, G. Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an EGFR-selective tyrosine kinase inhibitor. Clin. Cancer Res., 6: 2053-2063, 2000.
26. Ciardiello, F., Caputo, R., Borriello, G., Del Bufalo, D., Biroccio, A., Zupi, G., Bianco, A. R., and Tortora, G. ZD1839 ('Iressa'), an EGFR-selective tyrosine kinase inhibitor, enhances taxane activity in bcl-2 overexpressing, multidrug-resistant MCF-7 ADR human breast cancer cells. Int. J. Cancer, 98: 463-469, 2002.
27. Ciardiello, F., Caputo, R., Bianco, R., Damiano, V., Pomatico, G., Pepe, S., Bianco, A. R., Agrawal, S., Mendelsohn, J., and Tortora, G. Cooperative inhibition of renal cancer growth by anti-EGF receptor antibody and protein kinase A antisense oligonucleotide. J. Natl. Cancer Inst. (Bethesda), 90: 1087-1094, 1998.
28. Tortora, G., Caputo, R., Damiano, V., Bianco, R., Fontanini, G., Cuccato, S., De Placido, S., Bianco, A. R., and Ciardiello, F. Combined blockade of PKA and bcl-2 by antisense strategy induces apoptosis and inhibits tumor growth and angiogenesis. Clin. Cancer Res., 7: 2537-2544, 2001.
29. Padmapriya, A. A., Tang, J. Y., and Agrawal, S. Large-scale synthesis, purification, and analysis of oligodeoxynucleotide phosphorothioates. Antisense Res. Dev., 4: 185-199, 1994.
30. Olopade, O. I., Adeyanju, M. O., Safa, A. R., Hagos, F., Mick, R., Thompson, B., and Recant, W. M. Overexpression of BCL-x protein in primary breast cancer is associated with high tumor grade and nodal metastases. Cancer J. Sci. Am., 3: 230-237, 1997.
31. Schmitt, F. C., and Soares, R. TGFα and angiogenesis. Am. J. Surg. Pathol., 23: 358-359, 1999.
32. Bianco, C., Tortora, G., Baldassarre, G., Caputo, R., Fontanini, G., Chinè, S., Bianco, A. R., and Ciardiello, F. 8-chloro-cAMP inhibits autocrine and angiogenic growth factors production in human colorectal and breast cancer. Clin. Cancer Res., 3: 439-448, 1997.
33. Ciardiello, F., Caputo, R., Bianco, R., Damiano, V., Fontanini, G., Cuccato, S., De Placido, S., Bianco, A. R., and Tortora, G. Inhibition of growth factors production and angiogenesis in human cancer cells by ZD1839 (Iressa), a selective epidermal growth factor receptor tyrosine kinase inhibitor. Clin. Cancer Res., 7: 1459-1465, 2001.
34. Biroccio, A., Candiloro, A., Mottolese, M., Sapora, A., Albini, A., Zupi, G., and 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 cell line. FASEB J., 14: 652-660, 2000.
35. Fernandez, A., Udagawa, T., Schwesinger, C., Beecken, W., Achilles-Gerte, E., McDonnell, T., and D'Amato, R. Angiogenic potential of prostate carcinoma cells overexpressing bcl-2. J. Natl. Cancer Inst. (Bethesda), 93: 208-213, 2001.