Skip to main content
Top
Published in: Clinical & Experimental Metastasis 1/2013

01-01-2013 | Research Paper

Dipyridamole prevents triple-negative breast-cancer progression

Authors: Daniela Spano, Jean-Claude Marshall, Natascia Marino, Daniela De Martino, Alessia Romano, Maria Nunzia Scoppettuolo, Anna Maria Bello, Valeria Di Dato, Luigi Navas, Gennaro De Vita, Chiara Medaglia, Patricia S. Steeg, Massimo Zollo

Published in: Clinical & Experimental Metastasis | Issue 1/2013

Login to get access

Abstract

Dipyridamole is a widely prescribed drug in ischemic disorders, and it is here investigated for potential clinical use as a new treatment for breast cancer. Xenograft mice bearing triple-negative breast cancer 4T1-Luc or MDA-MB-231T cells were generated. In these in vivo models, dipyridamole effects were investigated for primary tumor growth, metastasis formation, cell cycle, apoptosis, signaling pathways, immune cell infiltration, and serum inflammatory cytokines levels. Dipyridamole significantly reduced primary tumor growth and metastasis formation by intraperitoneal administration. Treatment with 15 mg/kg/day dipyridamole reduced mean primary tumor size by 67.5 % (p = 0.0433), while treatment with 30 mg/kg/day dipyridamole resulted in an almost a total reduction in primary tumors (p = 0.0182). Experimental metastasis assays show dipyridamole reduces metastasis formation by 47.5 % in the MDA-MB-231T xenograft model (p = 0.0122), and by 50.26 % in the 4T1-Luc xenograft model (p = 0.0292). In vivo dipyridamole decreased activated β-catenin by 38.64 % (p < 0.0001), phospho-ERK1/2 by 25.05 % (p = 0.0129), phospho-p65 by 67.82 % (p < 0.0001) and doubled the expression of IkBα (p = 0.0019), thus revealing significant effects on Wnt, ERK1/2-MAPK and NF-kB pathways in both animal models. Moreover dipyridamole significantly decreased the infiltration of tumor-associated macrophages and myeloid-derived suppressor cells in primary tumors (p < 0.005), and the inflammatory cytokines levels in the sera of the treated mice. We suggest that when used at appropriate doses and with the correct mode of administration, dipyridamole is a promising agent for breast-cancer treatment, thus also implying its potential use in other cancers that show those highly activated pathways.
Appendix
Available only for authorised users
Literature
1.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90PubMedCrossRef Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90PubMedCrossRef
2.
go back to reference Steeg PS (2006) Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 12:895–904PubMedCrossRef Steeg PS (2006) Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 12:895–904PubMedCrossRef
3.
go back to reference Schaper W (2005) Dipyridamole, an underestimated vascular protective drug. Cardiovasc Drugs Ther 19:357–363PubMedCrossRef Schaper W (2005) Dipyridamole, an underestimated vascular protective drug. Cardiovasc Drugs Ther 19:357–363PubMedCrossRef
4.
go back to reference Belt JA, Marina NM, Phelps DA, Crawford CR (1993) Nucleoside transport in normal and neoplastic cells. Adv Enzyme Regul 33:235–252PubMedCrossRef Belt JA, Marina NM, Phelps DA, Crawford CR (1993) Nucleoside transport in normal and neoplastic cells. Adv Enzyme Regul 33:235–252PubMedCrossRef
5.
go back to reference Walling J (2006) From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates. Invest New Drugs 24:37–77PubMedCrossRef Walling J (2006) From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates. Invest New Drugs 24:37–77PubMedCrossRef
6.
go back to reference Howell SB, Hom D, Sanga R, Vick JS, Abramson IS (1989) Comparison of the synergistic potentiation of etoposide, doxorubicin, and vinblastine cytotoxicity by dipyridamole. Cancer Res 49:3178–3183PubMed Howell SB, Hom D, Sanga R, Vick JS, Abramson IS (1989) Comparison of the synergistic potentiation of etoposide, doxorubicin, and vinblastine cytotoxicity by dipyridamole. Cancer Res 49:3178–3183PubMed
7.
go back to reference Ramu N, Ramu A (1989) Circumvention of adriamycin resistance by dipyridamole analogues: a structure-activity relationship study. Int J Cancer 43:487–491PubMedCrossRef Ramu N, Ramu A (1989) Circumvention of adriamycin resistance by dipyridamole analogues: a structure-activity relationship study. Int J Cancer 43:487–491PubMedCrossRef
8.
go back to reference Lehman NL, Danenberg PV (2000) Modulation of RTX cytotoxicity by thymidine and dipyridamole in vitro: implications for chemotherapy. Cancer Chemother Pharmacol 45:142–148PubMedCrossRef Lehman NL, Danenberg PV (2000) Modulation of RTX cytotoxicity by thymidine and dipyridamole in vitro: implications for chemotherapy. Cancer Chemother Pharmacol 45:142–148PubMedCrossRef
9.
go back to reference Nelson JA, Drake S (1984) Potentiation of methotrexate toxicity by dipyridamole. Cancer Res 44:2493–2496PubMed Nelson JA, Drake S (1984) Potentiation of methotrexate toxicity by dipyridamole. Cancer Res 44:2493–2496PubMed
10.
go back to reference Desai PB, Sridhar R (1992) Potentiation of cytotoxicity of mitoxantrone toward CHO-K1 cells in vitro by dipyridamole. Pharm Res 9:178–181PubMedCrossRef Desai PB, Sridhar R (1992) Potentiation of cytotoxicity of mitoxantrone toward CHO-K1 cells in vitro by dipyridamole. Pharm Res 9:178–181PubMedCrossRef
11.
go back to reference Boyer CR, Karjian PL, Wahl GM, Pegram M, Neuteboom ST (2002) Nucleoside transport inhibitors, dipyridamole and p-nitrobenzylthioinosine, selectively potentiate the antitumor activity of NB1011. Anticancer Drugs 13:29–36PubMedCrossRef Boyer CR, Karjian PL, Wahl GM, Pegram M, Neuteboom ST (2002) Nucleoside transport inhibitors, dipyridamole and p-nitrobenzylthioinosine, selectively potentiate the antitumor activity of NB1011. Anticancer Drugs 13:29–36PubMedCrossRef
12.
go back to reference Rodrigues M, Barbosa F Jr, Perussi JR (2004) Dipyridamole increases the cytotoxicity of cisplatin in human larynx cancer cells in vitro. Braz J Med Biol Res 37:591–599PubMedCrossRef Rodrigues M, Barbosa F Jr, Perussi JR (2004) Dipyridamole increases the cytotoxicity of cisplatin in human larynx cancer cells in vitro. Braz J Med Biol Res 37:591–599PubMedCrossRef
13.
go back to reference Sato S, Kohno K, Hidaka K, Hisatsugu T, Kuwano M, Komiyama S (1993) Differentially potentiating effects by dipyridamole on cytotoxicity of 5-fluorouracil against three human maxillary cancer cell lines derived from a single tumor. Anticancer Drug Des 8:289–297PubMed Sato S, Kohno K, Hidaka K, Hisatsugu T, Kuwano M, Komiyama S (1993) Differentially potentiating effects by dipyridamole on cytotoxicity of 5-fluorouracil against three human maxillary cancer cell lines derived from a single tumor. Anticancer Drug Des 8:289–297PubMed
14.
go back to reference Kennedy DG, Van den Berg HW, Clarke R, Murphy RF (1986) Enhancement of methotrexate cytotoxicity towards the MDA.MB.436 human breast cancer cell line by dipyridamole. The role of methotrexate polyglutamates. Biochem Pharmacol 35:3053–3056PubMedCrossRef Kennedy DG, Van den Berg HW, Clarke R, Murphy RF (1986) Enhancement of methotrexate cytotoxicity towards the MDA.MB.436 human breast cancer cell line by dipyridamole. The role of methotrexate polyglutamates. Biochem Pharmacol 35:3053–3056PubMedCrossRef
15.
go back to reference Goda AE, Yoshida T, Horinaka M, Yasuda T, Shiraishi T, Wakada M, Sakai T (2008) Mechanisms of enhancement of TRAIL tumoricidal activity against human cancer cells of different origin by dipyridamole. Oncogene 27:3435–3445PubMedCrossRef Goda AE, Yoshida T, Horinaka M, Yasuda T, Shiraishi T, Wakada M, Sakai T (2008) Mechanisms of enhancement of TRAIL tumoricidal activity against human cancer cells of different origin by dipyridamole. Oncogene 27:3435–3445PubMedCrossRef
16.
go back to reference Zhang Y, Gupta A, Wang H, Zhou L, Vethanayagam RR, Unadkat JD, Mao Q (2005) BCRP transports dipyridamole and is inhibited by calcium channel blockers. Pharm Res 22:2023–2034PubMedCrossRef Zhang Y, Gupta A, Wang H, Zhou L, Vethanayagam RR, Unadkat JD, Mao Q (2005) BCRP transports dipyridamole and is inhibited by calcium channel blockers. Pharm Res 22:2023–2034PubMedCrossRef
17.
go back to reference Haimeur A, Conseil G, Deeley RG, Cole SP (2004) The MRP-related and BCRP/ABCG2 multidrug resistance proteins: biology, substrate specificity and regulation. Curr Drug Metab 5:21–53PubMedCrossRef Haimeur A, Conseil G, Deeley RG, Cole SP (2004) The MRP-related and BCRP/ABCG2 multidrug resistance proteins: biology, substrate specificity and regulation. Curr Drug Metab 5:21–53PubMedCrossRef
18.
go back to reference Eisert WG (2002) Dipyridamole. In: Michelson AD (ed) Platelets. Academic Press, Amsterdam, pp 803–815 Eisert WG (2002) Dipyridamole. In: Michelson AD (ed) Platelets. Academic Press, Amsterdam, pp 803–815
19.
go back to reference White H, Jamieson DG (2010) Review of the ESPRIT Study: aspirin plus dipyridamole versus aspirin alone for prevention of vascular events after a noncardioembolic, mild-to-moderate ischemic stroke or transient ischemic attack. Postgrad Med 122:227–229PubMedCrossRef White H, Jamieson DG (2010) Review of the ESPRIT Study: aspirin plus dipyridamole versus aspirin alone for prevention of vascular events after a noncardioembolic, mild-to-moderate ischemic stroke or transient ischemic attack. Postgrad Med 122:227–229PubMedCrossRef
20.
go back to reference Tsuruo T, Fujita N (2008) Platelet aggregation in the formation of tumor metastasis. Proc Jpn Acad Ser B Phys Biol Sci 84:189–198PubMedCrossRef Tsuruo T, Fujita N (2008) Platelet aggregation in the formation of tumor metastasis. Proc Jpn Acad Ser B Phys Biol Sci 84:189–198PubMedCrossRef
21.
go back to reference Nierodzik ML, Karpatkin S (2006) Thrombin induces tumor growth, metastasis, and angiogenesis: evidence for a thrombin-regulated dormant tumor phenotype. Cancer Cell 10:355–362PubMedCrossRef Nierodzik ML, Karpatkin S (2006) Thrombin induces tumor growth, metastasis, and angiogenesis: evidence for a thrombin-regulated dormant tumor phenotype. Cancer Cell 10:355–362PubMedCrossRef
22.
go back to reference Isacoff WH, Bendetti JK, Barstis JJ, Jazieh AR, Macdonald JS, Philip PA (2007) Phase II trial of infusional fluorouracil, leucovorin, mitomycin, and dipyridamole in locally advanced unresectable pancreatic adenocarcinoma: SWOG S9700. J Clin Oncol 25:1665–1669PubMedCrossRef Isacoff WH, Bendetti JK, Barstis JJ, Jazieh AR, Macdonald JS, Philip PA (2007) Phase II trial of infusional fluorouracil, leucovorin, mitomycin, and dipyridamole in locally advanced unresectable pancreatic adenocarcinoma: SWOG S9700. J Clin Oncol 25:1665–1669PubMedCrossRef
23.
go back to reference Raschko JW, Synold TW, Chow W, Coluzzi P, Hamasaki V, Leong LA, Margolin KA, Morgan RJ, Shibata SI, Somlo G, Tetef ML, Yen Y, ter Veer A, Doroshow JH (2000) A phase I study of carboplatin and etoposide administered in conjunction with dipyridamole, prochlorperazine and cyclosporine A. Cancer Chemother Pharmacol 46:403–410PubMedCrossRef Raschko JW, Synold TW, Chow W, Coluzzi P, Hamasaki V, Leong LA, Margolin KA, Morgan RJ, Shibata SI, Somlo G, Tetef ML, Yen Y, ter Veer A, Doroshow JH (2000) A phase I study of carboplatin and etoposide administered in conjunction with dipyridamole, prochlorperazine and cyclosporine A. Cancer Chemother Pharmacol 46:403–410PubMedCrossRef
24.
go back to reference Burch PA, Ghosh C, Schroeder G, Allmer C, Woodhouse CL, Goldberg RM, Addo F, Bernath AM, Tschetter LK, Windschitl HE, Cobau CD (2000) Phase II evaluation of continuous-infusion 5-fluorouracil, leucovorin, mitomycin-C, and oral dipyridamole in advanced measurable pancreatic cancer: a North Central Cancer Treatment Group Trial. Am J Clin Oncol 23:534–537PubMedCrossRef Burch PA, Ghosh C, Schroeder G, Allmer C, Woodhouse CL, Goldberg RM, Addo F, Bernath AM, Tschetter LK, Windschitl HE, Cobau CD (2000) Phase II evaluation of continuous-infusion 5-fluorouracil, leucovorin, mitomycin-C, and oral dipyridamole in advanced measurable pancreatic cancer: a North Central Cancer Treatment Group Trial. Am J Clin Oncol 23:534–537PubMedCrossRef
25.
go back to reference Wenzel J, Zeisig R, Fichtner I (2009) Inhibition of breast cancer metastasis by dual liposomes to disturb complex formation. Int J Pharm 370:121–128PubMedCrossRef Wenzel J, Zeisig R, Fichtner I (2009) Inhibition of breast cancer metastasis by dual liposomes to disturb complex formation. Int J Pharm 370:121–128PubMedCrossRef
26.
go back to reference Wenzel J, Zeisig R, Haider W, Habedank S, Fichtner I (2010) Inhibition of pulmonary metastasis in a human MT3 breast cancer xenograft model by dual liposomes preventing intravasal fibrin clot formation. Breast Cancer Res Treat 121:13–22PubMedCrossRef Wenzel J, Zeisig R, Haider W, Habedank S, Fichtner I (2010) Inhibition of pulmonary metastasis in a human MT3 breast cancer xenograft model by dual liposomes preventing intravasal fibrin clot formation. Breast Cancer Res Treat 121:13–22PubMedCrossRef
27.
go back to reference Foulkes WD, Smith IE, Reis-Filho JS (2010) Triple-negative breast cancer. N Engl J Med 363:1938–1948PubMedCrossRef Foulkes WD, Smith IE, Reis-Filho JS (2010) Triple-negative breast cancer. N Engl J Med 363:1938–1948PubMedCrossRef
28.
go back to reference Xing JZ, Zhu L, Gabos S, Xie L (2006) Microelectronic cell sensor assay for detection of cytotoxicity and prediction of acute toxicity. Toxicol in Vitro 20:995–1004PubMedCrossRef Xing JZ, Zhu L, Gabos S, Xie L (2006) Microelectronic cell sensor assay for detection of cytotoxicity and prediction of acute toxicity. Toxicol in Vitro 20:995–1004PubMedCrossRef
29.
go back to reference Spano D, Cimmino F, Capasso M, D’Angelo F, Zambrano N, Terracciano L, Iolascon A (2008) Changes of the hepatic proteome in hepatitis B-infected mouse model at early stages of fibrosis. J Proteome Res 7:2642–2653PubMedCrossRef Spano D, Cimmino F, Capasso M, D’Angelo F, Zambrano N, Terracciano L, Iolascon A (2008) Changes of the hepatic proteome in hepatitis B-infected mouse model at early stages of fibrosis. J Proteome Res 7:2642–2653PubMedCrossRef
30.
go back to reference Chuang KA, Lieu CH, Tsai WJ, Wu MH, Chen YC, Liao JF, Wang CC, Kuo YC (2010) Evaluation of anti-Wnt/β-catenin signaling agents by pGL4-TOP transfected stable cells with a luciferase reporter system. Braz J Med Biol Res 43:931–941PubMedCrossRef Chuang KA, Lieu CH, Tsai WJ, Wu MH, Chen YC, Liao JF, Wang CC, Kuo YC (2010) Evaluation of anti-Wnt/β-catenin signaling agents by pGL4-TOP transfected stable cells with a luciferase reporter system. Braz J Med Biol Res 43:931–941PubMedCrossRef
31.
go back to reference Vlad A, Röhrs S, Klein-Hitpass L, Müller O (2008) The first five years of the Wnt targetome. Cell Signal 20:795–802PubMedCrossRef Vlad A, Röhrs S, Klein-Hitpass L, Müller O (2008) The first five years of the Wnt targetome. Cell Signal 20:795–802PubMedCrossRef
32.
go back to reference Weyrich AS, Denis MM, Kuhlmann-Eyre JR, Spencer ED, Dixon DA, Marathe GK, McIntyre TM, Zimmerman GA, Prescott SM (2005) Dipyridamole selectively inhibits inflammatory gene expression in platelet-monocyte aggregates. Circulation 111:633–642PubMedCrossRef Weyrich AS, Denis MM, Kuhlmann-Eyre JR, Spencer ED, Dixon DA, Marathe GK, McIntyre TM, Zimmerman GA, Prescott SM (2005) Dipyridamole selectively inhibits inflammatory gene expression in platelet-monocyte aggregates. Circulation 111:633–642PubMedCrossRef
33.
go back to reference Chakrabarti S, Blair P, Wu C, Freedman JE (2007) Redox state of dipyridamole is a critical determinant for its beneficial antioxidant and antiinflammatory effects. J Cardiovasc Pharmacol 50:449–457PubMedCrossRef Chakrabarti S, Blair P, Wu C, Freedman JE (2007) Redox state of dipyridamole is a critical determinant for its beneficial antioxidant and antiinflammatory effects. J Cardiovasc Pharmacol 50:449–457PubMedCrossRef
34.
go back to reference Sethi G, Ahn KS, Sung B, Aggarwal BB (2008) Pinitol targets nuclear factor-kappaB activation pathway leading to inhibition of gene products associated with proliferation, apoptosis, invasion, and angiogenesis. Mol Cancer Ther 7:1604–1614PubMedCrossRef Sethi G, Ahn KS, Sung B, Aggarwal BB (2008) Pinitol targets nuclear factor-kappaB activation pathway leading to inhibition of gene products associated with proliferation, apoptosis, invasion, and angiogenesis. Mol Cancer Ther 7:1604–1614PubMedCrossRef
35.
go back to reference Kawakami H, Tomita M, Matsuda T, Ohta T, Tanaka Y, Fujii M, Hatano M, Tokuhisa T, Mori N (2005) Transcriptional activation of survivin through the NF-kappaB pathway by human T-cell leukemia virus type I tax. Int J Cancer 115:967–974PubMedCrossRef Kawakami H, Tomita M, Matsuda T, Ohta T, Tanaka Y, Fujii M, Hatano M, Tokuhisa T, Mori N (2005) Transcriptional activation of survivin through the NF-kappaB pathway by human T-cell leukemia virus type I tax. Int J Cancer 115:967–974PubMedCrossRef
36.
37.
go back to reference Boye K, Maelandsmo GM (2010) S100A4 and metastasis: a small actor playing many roles. Am J Pathol 176:528–535PubMedCrossRef Boye K, Maelandsmo GM (2010) S100A4 and metastasis: a small actor playing many roles. Am J Pathol 176:528–535PubMedCrossRef
38.
go back to reference Stein U, Arlt F, Walther W, Smith J, Waldman T, Harris ED, Mertins SD, Heizmann CW, Allard D, Birchmeier W, Schlag PM, Shoemaker RH (2006) The metastasis-associated gene S100A4 is a novel target of beta-catenin/T-cell factor signaling in colon cancer. Gastroenterology 131:1486–1500PubMedCrossRef Stein U, Arlt F, Walther W, Smith J, Waldman T, Harris ED, Mertins SD, Heizmann CW, Allard D, Birchmeier W, Schlag PM, Shoemaker RH (2006) The metastasis-associated gene S100A4 is a novel target of beta-catenin/T-cell factor signaling in colon cancer. Gastroenterology 131:1486–1500PubMedCrossRef
39.
go back to reference Grotterød I, Maelandsmo GM, Boye K (2010) Signal transduction mechanisms involved in S100A4-induced activation of the transcription factor NF-kappaB. BMC Cancer 10:241PubMedCrossRef Grotterød I, Maelandsmo GM, Boye K (2010) Signal transduction mechanisms involved in S100A4-induced activation of the transcription factor NF-kappaB. BMC Cancer 10:241PubMedCrossRef
40.
go back to reference Haskó G, Kuhel DG, Chen JF, Schwarzschild MA, Deitch EA, Mabley JG, Marton A, Szabó C (2000) Adenosine inhibits IL-12 and TNF-[alpha] production via adenosine A2a receptor-dependent and independent mechanisms. FASEB J 14:2065–2074PubMedCrossRef Haskó G, Kuhel DG, Chen JF, Schwarzschild MA, Deitch EA, Mabley JG, Marton A, Szabó C (2000) Adenosine inhibits IL-12 and TNF-[alpha] production via adenosine A2a receptor-dependent and independent mechanisms. FASEB J 14:2065–2074PubMedCrossRef
41.
go back to reference Budd GT, Jayaraj A, Grabowski D, Adelstein D, Bauer L, Boyett J, Bukowski R, Murthy S, Weick J (1990) Phase I trial of dipyridamole with 5-fluorouracil and folinic acid. Cancer Res 50:7206–7211PubMed Budd GT, Jayaraj A, Grabowski D, Adelstein D, Bauer L, Boyett J, Bukowski R, Murthy S, Weick J (1990) Phase I trial of dipyridamole with 5-fluorouracil and folinic acid. Cancer Res 50:7206–7211PubMed
42.
go back to reference Chakravarthy A, Abrams RA, Yeo CJ, Korman LT, Donehower RC, Hruban RH, Zahurek ML, Grochow LB, O’Reilly S, Hurwitz H, Jaffee EM, Lillemoe KD, Cameron JL (2000) Intensified adjuvant combined modality therapy for resected periampullary adenocarcinoma: acceptable toxicity and suggestion of improved 1-year disease-free survival. Int J Radiat Oncol Biol Phys 48:1089–1096PubMedCrossRef Chakravarthy A, Abrams RA, Yeo CJ, Korman LT, Donehower RC, Hruban RH, Zahurek ML, Grochow LB, O’Reilly S, Hurwitz H, Jaffee EM, Lillemoe KD, Cameron JL (2000) Intensified adjuvant combined modality therapy for resected periampullary adenocarcinoma: acceptable toxicity and suggestion of improved 1-year disease-free survival. Int J Radiat Oncol Biol Phys 48:1089–1096PubMedCrossRef
43.
go back to reference Willson JK, Fischer PH, Tutsch K, Alberti D, Simon K, Hamilton RD, Bruggink J, Koeller JM, Tormey DC, Earhart RH, Ranhosky A, Trump DL (1988) Phase I clinical trial of a combination of dipyridamole and acivicin based upon inhibition of nucleoside salvage. Cancer Res 48:5585–5590PubMed Willson JK, Fischer PH, Tutsch K, Alberti D, Simon K, Hamilton RD, Bruggink J, Koeller JM, Tormey DC, Earhart RH, Ranhosky A, Trump DL (1988) Phase I clinical trial of a combination of dipyridamole and acivicin based upon inhibition of nucleoside salvage. Cancer Res 48:5585–5590PubMed
44.
go back to reference Goel R, Cleary SM, Horton C, Balis FM, Zimm S, Kirmani S, Howell SB (1989) Selective intraperitoneal biochemical modulation of methotrexate by dipyridamole. J Clin Oncol 7:262–269PubMed Goel R, Cleary SM, Horton C, Balis FM, Zimm S, Kirmani S, Howell SB (1989) Selective intraperitoneal biochemical modulation of methotrexate by dipyridamole. J Clin Oncol 7:262–269PubMed
45.
go back to reference Isonishi S, Kirmani S, Kim S, Plaxe SC, Braly PS, McClay EF, Howell SB (1991) Phase I and pharmacokinetic trial of intraperitoneal etoposide in combination with the multidrug-resistance-modulating agent dipyridamole. J Natl Cancer Inst 83:621–626PubMedCrossRef Isonishi S, Kirmani S, Kim S, Plaxe SC, Braly PS, McClay EF, Howell SB (1991) Phase I and pharmacokinetic trial of intraperitoneal etoposide in combination with the multidrug-resistance-modulating agent dipyridamole. J Natl Cancer Inst 83:621–626PubMedCrossRef
46.
go back to reference Mahony C, Wolfram KM, Cocchetto DM, Bjornsson TD (1982) Dipyridamol kinetics. Clin Pharmacol Ther 31:330–338PubMedCrossRef Mahony C, Wolfram KM, Cocchetto DM, Bjornsson TD (1982) Dipyridamol kinetics. Clin Pharmacol Ther 31:330–338PubMedCrossRef
47.
go back to reference Curtin NJ, Bowman KJ, Turner RN, Huang B, Loughlin PJ, Calvert AH, Golding BT, Griffin RJ, Newell DR (1999) Potentiation of the cytotoxicity of thymidylate synthase (TS) inhibitors by dipyridamole analogues with reduced alpha1-acid glycoprotein binding. Br J Cancer 80:1738–1746PubMedCrossRef Curtin NJ, Bowman KJ, Turner RN, Huang B, Loughlin PJ, Calvert AH, Golding BT, Griffin RJ, Newell DR (1999) Potentiation of the cytotoxicity of thymidylate synthase (TS) inhibitors by dipyridamole analogues with reduced alpha1-acid glycoprotein binding. Br J Cancer 80:1738–1746PubMedCrossRef
48.
49.
go back to reference Kaler P, Godasi BN, Augenlicht L, Klampfer L (2009) The NF-kappaB/AKT-dependent Induction of Wnt Signaling in Colon Cancer Cells by Macrophages and IL-1beta. Cancer Microenviron 2:69–80CrossRef Kaler P, Godasi BN, Augenlicht L, Klampfer L (2009) The NF-kappaB/AKT-dependent Induction of Wnt Signaling in Colon Cancer Cells by Macrophages and IL-1beta. Cancer Microenviron 2:69–80CrossRef
50.
go back to reference Kim D, Rath O, Kolch W, Cho KH (2007) A hidden oncogenic positive feedback loop caused by crosstalk between Wnt and ERK pathways. Oncogene 26:4571–4579PubMedCrossRef Kim D, Rath O, Kolch W, Cho KH (2007) A hidden oncogenic positive feedback loop caused by crosstalk between Wnt and ERK pathways. Oncogene 26:4571–4579PubMedCrossRef
51.
go back to reference Chuderland D, Seger R (2005) Protein-protein interactions in the regulation of the extracellular signal-regulated kinase. Mol Biotechnol 29:57–74PubMedCrossRef Chuderland D, Seger R (2005) Protein-protein interactions in the regulation of the extracellular signal-regulated kinase. Mol Biotechnol 29:57–74PubMedCrossRef
52.
go back to reference Solinas G, Germano G, Mantovani A, Allavena P (2009) Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol 86:1065–1073PubMedCrossRef Solinas G, Germano G, Mantovani A, Allavena P (2009) Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol 86:1065–1073PubMedCrossRef
53.
54.
55.
go back to reference Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, Gutkovich-Pyest E, Urieli-Shoval S, Galun E, Ben-Neriah Y (2004) NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 431:461–466PubMedCrossRef Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, Gutkovich-Pyest E, Urieli-Shoval S, Galun E, Ben-Neriah Y (2004) NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 431:461–466PubMedCrossRef
Metadata
Title
Dipyridamole prevents triple-negative breast-cancer progression
Authors
Daniela Spano
Jean-Claude Marshall
Natascia Marino
Daniela De Martino
Alessia Romano
Maria Nunzia Scoppettuolo
Anna Maria Bello
Valeria Di Dato
Luigi Navas
Gennaro De Vita
Chiara Medaglia
Patricia S. Steeg
Massimo Zollo
Publication date
01-01-2013
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 1/2013
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-012-9506-0

Other articles of this Issue 1/2013

Clinical & Experimental Metastasis 1/2013 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine