Advertisement

Enhanced anticancer activity of combined treatment of imatinib and dipyridamole in solid Ehrlich carcinoma-bearing mice

  • Alaa E. El-Sisi
  • Samia S. Sokar
  • Hanaa A. IbrahimEmail author
  • Sally E. Abu-Risha
Original Article

Abstract

The current study was designed to evaluate potential enhancement of the anticancer activity of imatinib mesylate (IM) with dipyridamole (DIP) and to investigate the underlying mechanisms of the combined therapy (IM/DIP) to reduce hepatotoxicity of IM in solid Ehrlich carcinoma (SEC)-bearing mice. SEC was induced in female albino mice as a model for experimentally induced breast cancer. Mice were randomly divided into seven groups (n = 10): SEC vehicle, IM50 (50 mg/kg), IM100 (100 mg/kg), DIP (35 mg/kg), a combination of IM50/DIP and IM100/DIP. On day 28th, mice were sacrificed and blood samples were collected for hematological studies. Biochemical determination of liver markers was evaluated. Glutamic oxaloacetic transaminase (SGOT), glutamic pyruvic transaminase (SGPT) and alkaline phosphatase (ALP) levels were assessed. In addition, MDR-1 gene expression and immunohistochemical staining of BAX and BCL-2 was done. Also, in vitro experiment for determination of IC50 of different treatments and combination index (CI) were assessed in both MCF-7 and HCT-116 cell lines. IM- and/or DIP-treated groups showed a significant reduction in tumor volume, weight, and serum levels of SGOT, SGPT, and AIP compared to vehicle group. In addition, reduction of VEGF, Ki67, and adenosine contents was also reported by treated groups. Also, IM/DIP combination showed lower IC50 than monotherapy. Combination index is less than 1 for IM/DIP combination in both cell lines. DIP as an adjuvant therapy potentiated the cytotoxic effect of IM, ameliorated its hepatic toxicity, and showed synergistic effect with IM in vitro cell lines. Furthermore, the resistance against IM therapy may be overcome by the use of DIP independent on mdr-1 gene expression.

Keywords

Ehrlich carcinoma Imatinib Mesylate Dipyridamole Hepatotoxicity MDR-1, p-GP 

Notes

Acknowledgments

The authors acknowledge Dr. Mohammed Fawzy, professor of pathology, faculty of medicine, Mansoura University. Also, the authors acknowledge Dr. Eman G. Khedr, professor of Biochemistry, Faculty of Pharmacy, Tanta University; Dr. El-Zeiny M. Ebeid professor of Physical Chemistry, Faculty of Science, Tanta University; and prof. Abdel-Aziz A. Zidan, Zoology Department, Faculty of Science, Damanhour University, Egypt and also worked at Center of Excellence in cancer Research (CECR), Tanta University, Tanta, Egypt for their valuable assistance and evaluation of histopathological studies, biochemical and genetic work, respectively.

Authors’ contributions

El-Sisi and Sokar conceived and designed the experiments, conducted the experiments, analyzed the data, and composed the manuscript. Abu-Risha and Ibrahim contributed reagents, materials, and analysis tools. All the authors read and approved the final manuscript.

Compliance with ethical standards

The experimental work described in this study complies with guidelines for the care and the use of laboratory animals and the ethical principles adopted by the “Research Ethics Committee”, Faculty of pharmacy, Tanta University.

Conflict of interest

The authors declare that there are no conflicts of interest.

References

  1. Antonioli L, Blandizzi C, Pacher P, Haskó G (2013) Immunity, inflammation and cancer: a leading role for adenosine. Nat Rev Cancer 13:842–857CrossRefGoogle Scholar
  2. Arunasree KM, Roy KR, Anilkumar K, Aparna A, Reddy GV, Reddanna P (2008) Imatinib-resistant K562 cells are more sensitive to celecoxib, a selective COX-2 inhibitor: role of COX-2 and MDR-1. Leuk Res 32:855–864.  https://doi.org/10.1016/J.LEUKRES.2007.11.007 CrossRefPubMedGoogle Scholar
  3. Bertino P, Piccardi F, Porta C et al (2008) Imatinib Mesylate enhances therapeutic effects of gemcitabine in human malignant mesothelioma xenografts. Clin Cancer Res 14:541–548.  https://doi.org/10.1158/1078-0432.CCR-07-1388 CrossRefPubMedGoogle Scholar
  4. Bhardwaj B, Klassen J, Cossette N, Sterns E, Tuck A, Deeley R, Sengupta S, Elliott B (1996) Localization of platelet-derived growth factor beta receptor expression in the periepithelial stroma of human breast carcinoma. Clin Cancer Res 2:773–782PubMedGoogle Scholar
  5. Boyer T, Gonzales F, Barthélémy A et al (2019) Clinical significance of ABCB1 in acute myeloid leukemia: a comprehensive study. Cancers (Basel) 11:1323.  https://doi.org/10.3390/cancers11091323 CrossRefGoogle Scholar
  6. Burnstock G, Di Virgilio F (2013) Purinergic signalling and cancer. Purinergic Signal 9:491–540CrossRefGoogle Scholar
  7. Buttarello M, Plebani M (2008) Automated blood cell counts. Am J Clin Pathol 130:104–116.  https://doi.org/10.1309/EK3C7CTDKNVPXVTN CrossRefPubMedGoogle Scholar
  8. Buzaid AC, Alberts DS, Einspahr J, Mosley K, Peng YM, Tutsch K, Spears CP, Garewal HS (1989) Effect of dipyridamole on fluorodeoxyuridine cytotoxicity in vitro and in cancer patients. Cancer Chemother Pharmacol 25:124–130CrossRefGoogle Scholar
  9. Cao S, Zhen Y (1989) Potentiation of antimetabolite antitumor activity in vivo by dipyridamole and amphotericin B. Cancer Chemother Pharmacol 24:181–186.  https://doi.org/10.1007/BF00300240 CrossRefPubMedGoogle Scholar
  10. Cardoso HJ, Vaz CV, Correia S, Figueira MI, Marques R, Maia CJ, Socorro S (2015) Paradoxical and contradictory effects of imatinib in two cell line models of hormone-refractory prostate cancer. Prostate 75:923–935.  https://doi.org/10.1002/pros.22976 CrossRefPubMedGoogle Scholar
  11. Chiu C-F, Lai G-Y, Chen C-H, Chiu CC, Hung SW, Chang CF (2019) 6,7-Dihydroxy-2-(4′-hydroxyphenyl) naphthalene induces HCT116 cell apoptosis through activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway. Drug Des Devel Ther Volume 13:1609–1621.  https://doi.org/10.2147/DDDT.S193914 CrossRefGoogle Scholar
  12. Chou T-C, Talalay P (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzym Regul 22:27–55.  https://doi.org/10.1016/0065-2571(84)90007-4 CrossRefGoogle Scholar
  13. Choudhary S, Sood S, Wang H-CR (2014) Dipyridamole intervention of breast cell carcinogenesis. Mol Carcinog 53:243–252.  https://doi.org/10.1002/mc.21970 CrossRefPubMedGoogle Scholar
  14. Clark RSB, Kochanek PM, Watkins SC et al (2001) Caspase-3 mediated neuronal death after traumatic brain injury in rats. J Neurochem 74:740–753.  https://doi.org/10.1046/j.1471-4159.2000.740740.x CrossRefGoogle Scholar
  15. Cristofanilli M, Morandi P, Krishnamurthy S, Reuben JM, Lee BN, Francis D, Booser DJ, Green MC, Arun BK, Pusztai L, Lopez A, Islam R, Valero V, Hortobagyi GN (2008) Imatinib mesylate (Gleevec) in advanced breast cancer-expressing C-kit or PDGFR-beta: clinical activity and biological correlations. Ann Oncol Off J Eur Soc Med Oncol 19:1713–1719.  https://doi.org/10.1093/annonc/mdn352 CrossRefGoogle Scholar
  16. Damaraju VL, Kuzma M, Mowles D, Cass CE, Sawyer MB (2015) Interactions of multitargeted kinase inhibitors and nucleoside drugs: Achilles heel of combination therapy? Mol Cancer Ther 14:236–245.  https://doi.org/10.1158/1535-7163.MCT-14-0337 CrossRefPubMedGoogle Scholar
  17. Declèves X, Bihorel S, Debray M et al (2008) ABC transporters and the accumulation of imatinib and its active metabolite CGP74588 in rat C6 glioma cells. Pharmacol Res 57:214–222.  https://doi.org/10.1016/j.phrs.2008.01.006 CrossRefPubMedGoogle Scholar
  18. Deininger MWN, O’Brien SG, Ford JM, Druker BJ (2003) Practical management of patients with chronic myeloid leukemia receiving imatinib. J Clin Oncol 21:1637–1647.  https://doi.org/10.1200/JCO.2003.11.143 CrossRefPubMedGoogle Scholar
  19. Ferrara N (2002) Role of vascular endothelial growth factor in physiologic and pathologic angiogenesis: therapeutic implications. Semin Oncol 29:10–14.  https://doi.org/10.1016/S0093-7754(02)70064-X CrossRefPubMedGoogle Scholar
  20. Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical Progress. Endocr Rev 25:581–611.  https://doi.org/10.1210/er.2003-0027 CrossRefPubMedGoogle Scholar
  21. Fisher DE (1994) Apoptosis in cancer therapy: crossing the threshold. Cell 78:539–542.  https://doi.org/10.1016/0092-8674(94)90518-5 CrossRefPubMedGoogle Scholar
  22. Gao JZ, Wang YL, Li J, Wei LX (2015) Effects of VEGF/VEGFR/K-ras signaling pathways on miRNA21 levels in hepatocellular carcinoma tissues in rats. Genet Mol Res 14:671–679.  https://doi.org/10.4238/2015.January.30.10 CrossRefPubMedGoogle Scholar
  23. Goda AE, Yoshida T, Horinaka M, Yasuda T, Shiraishi T, Wakada M, Sakai T et al (2008) Mechanisms of enhancement of TRAIL tumoricidal activity against human cancer cells of different origin by dipyridamole. Oncogene 27:3435–3445.  https://doi.org/10.1038/sj.onc.1211008 CrossRefPubMedGoogle Scholar
  24. Goda AE, Kim B-Y, Erikson RL et al (2014) Preclinical evaluation of bortezomib/dipyridamole novel combination as a potential therapeutic modality for hematologic malignancies. Mol Oncol 9:309–322.  https://doi.org/10.1016/j.molonc.2014.08.010 CrossRefPubMedPubMedCentralGoogle Scholar
  25. Gordon T (1993) Factors associated with serum alkaline phosphatase level. Arch Pathol Lab Med 117:187–190PubMedGoogle Scholar
  26. Greaves M, Maley CC (2012) Clonal evolution in cancer. Nature 481:306–313.  https://doi.org/10.1038/nature10762 CrossRefPubMedPubMedCentralGoogle Scholar
  27. Gulati GL, Hyun BH (1994) The automated CBC. A current perspective. Hematol Oncol Clin North Am 8:593–603CrossRefGoogle Scholar
  28. Haimeur A, Conseil G, Deeley RG, Cole SPC (2004) The MRP-related and BCRP/ABCG2 multidrug resistance proteins: biology, substrate specificity and regulation. Curr Drug Metab 5:21–53.  https://doi.org/10.2174/1389200043489199 CrossRefPubMedGoogle Scholar
  29. Haines DM, Chelack BJ (1991) Technical considerations for developing enzyme immunohistochemical staining procedures on formalin-fixed paraffin-embedded tissues for diagnostic pathologyGoogle Scholar
  30. Harker LA, Kadatz RA (1983) Mechanism of action of dipyridamole. Thromb Res Suppl 4:39–46CrossRefGoogle Scholar
  31. Huang H-Y, Huang W-W, Lin C-N, Eng HL, Li SH, Li CF, Lu D, Yu SC, Hsiung CY (2006a) Immunohistochemical expression of p16INK4A, Ki-67, and Mcm2 proteins in gastrointestinal stromal tumors: prognostic implications and correlations with risk stratification of NIH consensus criteria. Ann Surg Oncol 13:1633–1644.  https://doi.org/10.1245/s10434-006-9188-4 CrossRefPubMedGoogle Scholar
  32. Huang X-J, Choi Y-K, Im H-S et al (2006b) Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) detection techniques. Sensors (Basel) 6:756CrossRefGoogle Scholar
  33. 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 25:1665–1669.  https://doi.org/10.1200/JCO.2006.06.7637 CrossRefPubMedGoogle Scholar
  34. Iuliano L, Violl F, Ghiselli A, Alessandri C, Balsano F (1989) Dipyridamole inhibits lipid peroxidation and scavenges oxygen radicals. Lipids 24:430–433.  https://doi.org/10.1007/BF02535151 CrossRefGoogle Scholar
  35. Khedr NF, Khalil RM (2015) Effect of hesperidin on mice bearing Ehrlich solid carcinoma maintained on doxorubicin. Tumor Biol 36:9267–9275.  https://doi.org/10.1007/s13277-015-3655-0 CrossRefGoogle Scholar
  36. Klein CL, Wagner M, Kirkpatrick CJ, Van Kooten TG (2000) A new quantitative test method for cell proliferation based on detection of the Ki-67 protein. J Mater Sci Mater Med 11:125–132.  https://doi.org/10.1023/A:1008953319485 CrossRefPubMedGoogle Scholar
  37. Koga M, Hiromatsu Y, Jimi A et al (1999) Immunohistochemical analysis of Bcl-2, Bax, and Bak expression in thyroid glands from patients with subacute thyroiditis. J Clin Endocrinol Metab 84:2221–2225.  https://doi.org/10.1210/jcem.84.6.5748 CrossRefPubMedGoogle Scholar
  38. Kondo S, Tamura Y, Bawden JW, Tanase S (2001) The immunohistochemical localization of Bax and Bcl-2 and their relation to apoptosis during amelogenesis in developing rat molars. Arch Oral Biol 46:557–568.  https://doi.org/10.1016/S0003-9969(00)00139-4 CrossRefPubMedGoogle Scholar
  39. Krishan A, Sridhar KS, Mou C, Stein WD, Lyubimov E, Hu YP, Fernandez H (2000) Synergistic effect of prochlorperazine and dipyridamole on the cellular retention and cytotoxicity of doxorubicin. Clin Cancer Res 6:1508–1517PubMedGoogle Scholar
  40. Legros L, Bourcier C, Jacquel A, Mahon FX, Cassuto JP, Auberger P, Pagès G (2004) Imatinib mesylate (STI571) decreases the vascular endothelial growth factor plasma concentration in patients with chronic myeloid leukemia. Blood 104:495–501.  https://doi.org/10.1182/blood-2003-08-2695 CrossRefPubMedGoogle Scholar
  41. Leithner A, Gapp M, Radl R et al (2005) Immunohistochemical analysis of desmoid tumours. J Clin Pathol 58:1152–1156.  https://doi.org/10.1136/jcp.2005.026278 CrossRefPubMedPubMedCentralGoogle Scholar
  42. Liu X-J, Zheng Y-B, Li Y, Wu SY, Zhen YS (2014) A multifunctional drug combination shows highly potent therapeutic efficacy against human cancer xenografts in athymic mice. PLoS One 9:e115790.  https://doi.org/10.1371/journal.pone.0115790 CrossRefPubMedPubMedCentralGoogle Scholar
  43. Magiorakos A-P, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, Harbarth S, Hindler JF, Kahlmeter G, Olsson-Liljequist B, Paterson DL, Rice LB, Stelling J, Struelens MJ, Vatopoulos A, Weber JT, Monnet DL (2012) Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18:268–281.  https://doi.org/10.1111/j.1469-0691.2011.03570.x CrossRefGoogle Scholar
  44. Mahon F-X, Belloc F, Lagarde V, Chollet C, Moreau-Gaudry F, Reiffers J, Goldman JM, Melo JV (2003) MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood 101:2368–2373.  https://doi.org/10.1182/blood.V101.6.2368 CrossRefPubMedGoogle Scholar
  45. Mediavilla-Varela M, Luddy K, Noyes D, Khalil FK, Neuger AM, Soliman H, Antonia SJ (2013) Antagonism of adenosine A2A receptor expressed by lung adenocarcinoma tumor cells and cancer associated fibroblasts inhibits their growth. Cancer Biol Ther 14:860–868.  https://doi.org/10.4161/cbt.25643 CrossRefPubMedPubMedCentralGoogle Scholar
  46. MENG X, ZHANG Q, ZHENG G et al (2014) Doxorubicin combined with celecoxib inhibits tumor growth of medullary thyroid carcinoma in xenografted mice. Oncol Lett 7:2053–2058.  https://doi.org/10.3892/ol.2014.2050 CrossRefPubMedPubMedCentralGoogle Scholar
  47. Mfengwana PH, Mashele SS, Manduna IT (2019) Cytotoxicity and cell cycle analysis of Asparagus laricinus Burch. and Senecio asperulus DC. on breast and prostate cancer cell lines. Heliyon 5:e01666.  https://doi.org/10.1016/j.heliyon.2019.e01666 CrossRefPubMedPubMedCentralGoogle Scholar
  48. Mickley LA, Spengler BA, Knutsen TA, Biedler JL, Fojo T (1997) Gene rearrangement: a novel mechanism for MDR-1 gene activation. J Clin Invest 99:1947–1957.  https://doi.org/10.1172/JCI119362 CrossRefPubMedPubMedCentralGoogle Scholar
  49. Mikami J, Kurokawa Y, Takahashi T, Miyazaki Y, Yamasaki M, Miyata H, Nakajima K, Takiguchi S, Mori M, Doki Y (2016) Antitumor effect of antiplatelet agents in gastric cancer cells: an in vivo and in vitro study. Gastric Cancer 19:817–826.  https://doi.org/10.1007/s10120-015-0556-2 CrossRefPubMedGoogle Scholar
  50. Minden MD, Pong JT, Yu R et al (2014) Immediate utility of two approved agents to target both the metabolic mevalonate pathway and its restorative feedback loop. Cancer Res 74:4772–4782.  https://doi.org/10.1158/0008-5472.can-14-0130 CrossRefPubMedGoogle Scholar
  51. Mirza A, Basso A, Black S, Malkowski M, Kwee L, Pachter JA, Lachowicz JE, Wang Y, Liu S (2005) RNA interference targeting of A1 receptor-overexpressing breast carcinoma cells leads to diminished rates of cell proliferation and induction of apoptosis. Cancer Biol Ther 4:1355–1360.  https://doi.org/10.4161/cbt.4.12.2196 CrossRefPubMedGoogle Scholar
  52. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63.  https://doi.org/10.1016/0022-1759(83)90303-4 CrossRefGoogle Scholar
  53. Napolitano AP, Dean DM, Man AJ, Youssef J, Ho DN, Rago AP, Lech MP, Morgan JR (2007) Scaffold-free three-dimensional cell culture utilizing micromolded nonadhesive hydrogels. Biotechniques 43:494–500.  https://doi.org/10.2144/000112591 CrossRefPubMedGoogle Scholar
  54. Negi LM, Talegaonkar S, Jaggi M, Verma AK (2019) Hyaluronated imatinib liposomes with hybrid approach to target CD44 and P-gp overexpressing MDR cancer: an in-vitro , in-vivo and mechanistic investigation. J Drug Target 27:183–192.  https://doi.org/10.1080/1061186X.2018.1497039 CrossRefPubMedGoogle Scholar
  55. Nejime N, Tanaka N, Yoshihara R et al (2008) Effect of P2 receptor on the intracellular calcium increase by cancer cells in human umbilical vein endothelial cells. Naunyn Schmiedebergs Arch Pharmacol:429–436CrossRefGoogle Scholar
  56. Ohta A, Gorelik E, Prasad SJ, Ronchese F, Lukashev D, Wong MK, Huang X, Caldwell S, Liu K, Smith P, Chen JF, Jackson EK, Apasov S, Abrams S, Sitkovsky M (2006) A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci U S A 103:13132–13137.  https://doi.org/10.1073/pnas.0605251103 CrossRefPubMedPubMedCentralGoogle Scholar
  57. Osman AE-MM, Ahmed MMS, Khayyal MTE-D, El-Merzabani MM (1993) Hyperthermic potentiation of cisplatin cytotoxicity on solid Ehrlich carcinoma. Tumori J 79:268–272.  https://doi.org/10.1177/030089169307900408 CrossRefGoogle Scholar
  58. Ozaslan M, Karagoz I, Kilic I, Guldur M (2002) African journal of biotechnology. Academic JournalsGoogle Scholar
  59. Pérez-López ME, García-Gómez J, Alves MT, Paradela A, García-Mata J, García-Caballero T (2016) Ki-67 is a prognostic marker for hormone receptor positive tumors. Clin Transl Oncol 18:996–1002.  https://doi.org/10.1007/s12094-015-1472-y CrossRefPubMedPubMedCentralGoogle Scholar
  60. Perussi JR, Paltoo DN, Toppin VAL, Canada RG (2003) Synergism between dipyridamole and cisplatin in human breast cancer cells in vitro. Quim Nova 26:340–343.  https://doi.org/10.1590/S0100-40422003000300010 CrossRefGoogle Scholar
  61. Rahman A, Makpol S, Jamal R, Harun R, Mokhtar N, Ngah WZ (2014) Tocotrienol-rich fraction, [6]-Gingerol and epigallocatechin gallate inhibit proliferation and induce apoptosis of glioma cancer cells. Molecules 19:14528–14541.  https://doi.org/10.3390/molecules190914528 CrossRefPubMedPubMedCentralGoogle Scholar
  62. Raimondi C, Fantin A, Lampropoulou A et al (2014) Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1–dependent ABL1 activation in endothelial cells. J Exp Med 211:1167–1183.  https://doi.org/10.1084/JEM.20132330 CrossRefPubMedPubMedCentralGoogle Scholar
  63. Rodrigues M, Barbosa Junior F, Perussi JR (2004) Dipyridamole increases the cytotoxicity of cisplatin in human larynx cancer cells in vitro. Brazilian J Med Biol Res 37:591–599.  https://doi.org/10.1590/S0100-879X2004000400017 CrossRefGoogle Scholar
  64. Rosenberg IL, Russell CW, Giles GR (1978) Cell viability studies on the exfoliated colonic cancer cell. Br J Surg 65:188–190.  https://doi.org/10.1002/bjs.1800650314 CrossRefPubMedGoogle Scholar
  65. Rosenzweig SA (2018) Acquired resistance to drugs targeting tyrosine kinases. Adv Cancer Res:71–98Google Scholar
  66. Roussidis AE, Mitropoulou TN, Theocharis AD, Kiamouris C, Papadopoulos S, Kletsas D, Karamanos NK (2004) STI571 as a potent inhibitor of growth and invasiveness of human epithelial breast cancer cells. Anticancer Res 24:1445–1447PubMedGoogle Scholar
  67. Seidel J, Irion D, Henning F et al (1992) Kinetic measurement of GPT with the microtiter plate. Beitr Infusionsther 30:70–72PubMedGoogle Scholar
  68. Shalinsky D, Slovak M, Howell S (1991) Modulation of vinblastine sensitivity by dipyridamole in multidrug resistant fibrosarcoma cells lacking mdr1 expression. Br J Cancer 64:705–709.  https://doi.org/10.1038/bjc.1991.385 CrossRefPubMedPubMedCentralGoogle Scholar
  69. Shalinsky D, Howell S, Khatibi S et al (2011) Regulation of initial vinblastine influx by P-glycoprotein. Br J Cancer 67:30–36.  https://doi.org/10.1038/bjc.1993.6 CrossRefGoogle Scholar
  70. Shimada H, Chatten J, Newton WA et al (1984) Histopathologic prognostic factors in neuroblastic tumors: definition of subtypes of ganglioneuroblastoma and an age-linked classification of neuroblastomas. JNCI J Natl Cancer Inst 73:405–416.  https://doi.org/10.1093/jnci/73.2.405 CrossRefPubMedGoogle Scholar
  71. Smith PG, Marshman E, Newell DR, Curtin NJ (2000) Dipyridamole potentiates the in vitro activity of MTA (LY231514) by inhibition of thymidine transport. Br J Cancer 82:924–930.  https://doi.org/10.1054/bjoc.1999.1020 CrossRefPubMedPubMedCentralGoogle Scholar
  72. Sorrentino C, Morello S (2017) Role of adenosine in tumor progression: focus on A2B receptor as potential therapeutic target. J Cancer Metastasis Treat 3:127.  https://doi.org/10.20517/2394-4722.2017.29 CrossRefGoogle Scholar
  73. Soule HD, Vazquez J, Long A et al (1973) A human cell line from a pleural effusion derived from a breast carcinoma 2. JNCI J Natl Cancer Inst 51:1409–1416.  https://doi.org/10.1093/jnci/51.5.1409 CrossRefPubMedGoogle Scholar
  74. Spano D, Marshall J-C, Marino N, de Martino D, Romano A, Scoppettuolo MN, Bello AM, di Dato V, Navas L, de Vita G, Medaglia C, Steeg PS, Zollo M (2013) Dipyridamole prevents triple-negative breast-cancer progression. Clin Exp Metastasis 30:47–68.  https://doi.org/10.1007/s10585-012-9506-0 CrossRefPubMedGoogle Scholar
  75. Stagg J, Divisekera U, McLaughlin N, Sharkey J, Pommey S, Denoyer D, Dwyer KM, Smyth MJ (2010) Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis. Proc Natl Acad Sci U S A 107:1547–1552.  https://doi.org/10.1073/pnas.0908801107 CrossRefPubMedPubMedCentralGoogle Scholar
  76. Sumida T, Kitadai Y, Shinagawa K, Tanaka M, Kodama M, Ohnishi M, Ohara E, Tanaka S, Yasui W, Chayama K (2011) Anti-stromal therapy with imatinib inhibits growth and metastasis of gastric carcinoma in an orthotopic nude mouse model. Int J Cancer 128:2050–2062.  https://doi.org/10.1002/ijc.25812 CrossRefPubMedGoogle Scholar
  77. Sureechatchaiyan P, Hamacher A, Brockmann N, Stork B, Kassack MU (2018) Adenosine enhances cisplatin sensitivity in human ovarian cancer cells. Purinergic Signal 14:395–408.  https://doi.org/10.1007/s11302-018-9622-7 CrossRefPubMedPubMedCentralGoogle Scholar
  78. Szakács G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM (2006) Targeting multidrug resistance in cancer. Nat Rev Drug Discov 5:219–234.  https://doi.org/10.1038/nrd1984 CrossRefPubMedGoogle Scholar
  79. Turner RN, Aherne GW, Curtin NJ (2014) Selective potentiation of lometrexol growth inhibition by dipyridamole through cell-specific inhibition of hypoxanthine salvage.  https://doi.org/10.1038/bjc.1997.552 CrossRefGoogle Scholar
  80. van Meerloo J, Kaspers GJL, Cloos J (2011) Cell sensitivity assays: the MTT assay. Methods Mol Biol:237–245Google Scholar
  81. Villamil AG, Gadano AC, Mandó OG et al (2017) Imatinib-induced fatal acute liver failure. World J Gastroenterol 13:6608.  https://doi.org/10.3748/wjg.v13.i48.6608 CrossRefGoogle Scholar
  82. Wang C, Schwab LP, Fan M, Seagroves TN, Buolamwini JK (2013) Chemoprevention activity of dipyridamole in the MMTV-PyMT transgenic mouse model of breast cancer. Cancer Prev Res 6:437–447.  https://doi.org/10.1158/1940-6207.CAPR-12-0345 CrossRefGoogle Scholar
  83. Wang J, Wang L, Long L et al (2019) Solitary renal metastasis from squamous cell carcinoma of the lung: a case report. Medicine (Baltimore) 98.  https://doi.org/10.1097/MD.0000000000014310 CrossRefGoogle Scholar
  84. Wei Q, Zhang D, Yao A et al (2012) Design, synthesis, and in vitro and in vivo biological studies of a 3′-deoxythymidine conjugate that potentially kills cancer cells selectively. PLoS One 7.  https://doi.org/10.1371/journal.pone.0052199 CrossRefGoogle Scholar
  85. Weigel MT, Dahmke L, Schem C, Bauerschlag DO, Weber K, Niehoff P, Bauer M, Strauss A, Jonat W, Maass N, Mundhenke C (2010) In vitro effects of imatinib mesylate on radiosensitivity and chemosensitivity of breast cancer cells. BMC Cancer 10:412.  https://doi.org/10.1186/1471-2407-10-412 CrossRefPubMedPubMedCentralGoogle Scholar
  86. Wu G, Lu J, Guo J, et al (2013) Synergistic anti-cancer activity of the combination of dihydroartemisinin and doxorubicin in breast cancer cells. 453–459Google Scholar
  87. Yamakawa Y, Hamada A, Uchida T, Sato D, Yuki M, Hayashi M, Kawaguchi T, Saito H (2014) Distinct interaction of nilotinib and imatinib with P-glycoprotein in intracellular accumulation and cytotoxicity in CML cell line K562 cells. Biol Pharm Bull 37:1330–1335CrossRefGoogle Scholar
  88. Yao JC, Zhang JX, Rashid A et al (2007) Clinical and in vitro studies of Imatinib in advanced carcinoid tumors. Clin Cancer Res 13:234–240.  https://doi.org/10.1158/1078-0432.CCR-06-1618 CrossRefPubMedGoogle Scholar
  89. Yerushalmi R, Woods R, Ravdin PM et al (2010) Ki67 in breast cancer: prognostic and predictive potential. Lancet Oncol 11:174–183.  https://doi.org/10.1016/S1470-2045(09)70262-1 CrossRefPubMedGoogle Scholar
  90. 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 22:2023–2034.  https://doi.org/10.1007/s11095-005-8384-4 CrossRefPubMedGoogle Scholar
  91. Zhang WW, Cortes JE, Yao H, Zhang L, Reddy NG, Jabbour E, Kantarjian HM, Jones D (2009) Predictors of primary imatinib resistance in chronic myelogenous leukemia are distinct from those in secondary imatinib resistance. J Clin Oncol 27:3642–3649.  https://doi.org/10.1200/JCO.2008.19.4076 CrossRefPubMedPubMedCentralGoogle Scholar
  92. Zhou S, Xu H, Tang Q et al (2019) Dipyridamole enhances the cytotoxicities of the trametinib against colon cancer cells through combined targeting HMGCS1 and MEK pathway. Mol Cancer Ther.  https://doi.org/10.1158/1535-7163.MCT-19-0413 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  • Alaa E. El-Sisi
    • 1
  • Samia S. Sokar
    • 1
  • Hanaa A. Ibrahim
    • 1
    Email author
  • Sally E. Abu-Risha
    • 1
  1. 1.Department of Pharmacology and Toxicology, college of pharmacyUniversity of TantaTantaEgypt

Personalised recommendations