Purine analog-like properties of bendamustine underlie rapid activation of DNA damage response and synergistic effects with pyrimidine analogues in lymphoid malignancies

PLoS ONE

Volumn 9, Issue 3, 2014, Pages

  Hiraoka, Nobuya ^a   Kikuchi, Jiro ^a   Yamauchi, Takahiro ^b   Koyama, Daisuke ^a   Wada, Taeko ^a   Uesawa, Mitsuyo ^c   Akutsu, Miyuki ^c   Mori, Shigehisa ^d   Nakamura, Yuichi ^d   Ueda, Takanori ^b   Kano, Yasuhiko ^c   Furukawa, Yusuke ^a  

^a JICHI MEDICAL UNIVERSITY   (Japan)

^b UNIVERSITY OF FUKUI   (Japan)

^c TOCHIGI CANCER CENTER   (Japan)

^d SAITAMA MEDICAL UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; ALKYLATING AGENT; BENDAMUSTINE; BORTEZOMIB; CHLORAMBUCIL; CYTARABINE; CYTARABINE TRIPHOSPHATE; DEXAMETHASONE; DOXORUBICIN; EQUILIBRATIVE NUCLEOSIDE TRANSPORTER; ETOPOSIDE; FLUDARABINE; GEMCITABINE; MELPHALAN; MESSENGER RNA; METHOTREXATE; MITOXANTRONE; PERFOSFAMIDE; PYRIMIDINE DERIVATIVE; ROMIDEPSIN; VINCRISTINE; ANTINEOPLASTIC AGENT; CYCLOPHOSPHAMIDE; PYRIMIDINE; RITUXIMAB;

ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CELL CYCLE ARREST; CELL CYCLE G1 PHASE; CELL CYCLE S PHASE; CELL TRANSPORT; CONCENTRATION RESPONSE; CONTROLLED STUDY; DNA DAMAGE; DRUG ANTAGONISM; DRUG POTENTIATION; DRUG UPTAKE; HUMAN; HUMAN CELL; IC 50; LARGE CELL LYMPHOMA; LYMPHOMA; MANTLE CELL LYMPHOMA; MULTIDRUG RESISTANCE; MULTIPLE MYELOMA; NONHUMAN; NUCLEOSIDE TRANSPORT; PROTEIN EXPRESSION; RAT; ANALOGS AND DERIVATIVES; CELL CYCLE; CELL PROLIFERATION; CHEMISTRY; DOSE RESPONSE; DRUG EFFECTS; DRUG SCREENING; IC50; PATHOLOGY; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS, ALKYLATING; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BENDAMUSTINE HYDROCHLORIDE; CELL CYCLE; CELL LINE, TUMOR; CELL PROLIFERATION; CYCLOPHOSPHAMIDE; CYTARABINE; DNA DAMAGE; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG SCREENING ASSAYS, ANTITUMOR; DRUG SYNERGISM; HUMANS; INHIBITORY CONCENTRATION 50; LYMPHOMA; LYMPHOMA, LARGE B-CELL, DIFFUSE; LYMPHOMA, MANTLE-CELL; MULTIPLE MYELOMA; PYRIMIDINES; RITUXIMAB;

EID: 84898765095     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0090675     Document Type: Article

References (50)

1. Tageja N, Nagi J (2010) Bendamustine: something old, something new. Cancer Chemother Pharmacol 66: 413-423.
2. Hartmann M, Zimmer C (1972) Investigation of cross-link formation in DNA by the alkylating cytostatic IMET 3106, 3393 and 3943. Biochim Biophys Acta 287: 386-389.
3. Strumberg D, Harstrick A, Doll K, Hoffmann B, Seeber S (1996) Bendamustine hydrochloride activity against doxorubicin-resistant human breast carcinoma cell lines. Anticancer Drugs 7: 415-421. (Pubitemid 26249195)
4. Leoni LM, Bailey B, Reifert J, Bendall HH, Zeller RW, et al. (2008) Bendamustine (Treanda) displays a distinct pattern of cytotoxicity and unique mechanistic features compared with other alkylating agents. Clin Cancer Res 14: 309-317. (Pubitemid 351378007)
5. Schwänen C, Hecker T, Hübinger G, Wölfle M, Ritgen W, et al. (2002) In vitro evaluation of bendamustine induced apoptosis in B-chronic lymphocytic leukemia. Leukemia 16: 2096-2105. (Pubitemid 35203454)
6. Roué G, López-Guerra M, Milpied P, Pérez- Galán P, Villamor N, et al. (2008) Bendamustine is effective in p53-deficient B-cell neoplasms and requires oxidative stress and caspase-independent signaling. Clin Cancer Res 14: 6907-6915.
7. Beeharry N, Rattner JB, Bellacosa A, Smith MR, Yen TJ (2012) Dose dependent effects on cell cycle checkpoints and DNA repair by bendamustine. PLoS ONE 7: e40342.
8. Knauf WU, Lissichkov T, Aldaoud A, Liberati A, Loscertales J, et al. (2009) Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol 27: 4378-4384.
9. Friedberg JW, Cohen P, Chen L, Robinson KS, Forero-Torres A, et al. (2008) Bendamustine in patients with rituximab-refractory indolent and transformed non-Hodgkin's lymphoma: results from a phase II multicenter, single-agent study. J Clin Oncol 26: 204-210.
10. Robinson KS, Williams ME, van der Jagt RH, Cohen P, Herst JA, et al. (2008) Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin's lymphoma. J Clin Oncol 26: 4473-4479.
11. Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, et al. (2013) Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicetre, randomised, phase 3 non-inferiority trial. Lancet 381: 1203-1210.
12. Ohmachi K, Niitsu N, Uchida T, Kim SJ, Ando K, et al. (2013) Multicenter phase II study of bendamustine plus rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. J. Clin Oncol 31: 2103-2109.
13. McCloskey JK, Broome CM, Cheson BD (2013) Safe and effective treatment of aggressive non-Hodgkin lymphoma with rituximab and bendamustine in patients with severe liver impairment. Clin Adv Hematol Oncol 11: 184-188.
14. Hitz F, Fisher N, Pabst Th, Casper C, Berthod G, et al. (2013) Rituximab, bendamustine, and lenalidomide in patients with aggressive B cell lymphoma not eligible for high-dose chemotherapy or anthracycline-based therapy: phase I results of the SAKK 38/08 trial. Ann Hematol 92: 1033-1040.
15. Lentzsch S, O'Sullivan A, Kennedy RC, Abbas M, Dai L, et al. (2012) Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study. Blood 119: 4608-4613.
16. Offidani M, Corvatta L, Maracci L, Liberati AM, Ballanti S, et al. (2013) Efficacy and tolerability of bendamustine, bortezomib and dexamethasone in patients with relapsed-refractory multiple myeloma: a phase II study. Blood Cancer J 3: e162.
17. Damaj G, Gressin R, Bouabdallah K, Cartron G, Choufi B, et al. (2013) Results from a prospective, open-label, phase II trial of bendamustine in refractory or relapsed T-cell lymphomas: the BENTLY trial. J Clin Oncol 31: 104-110.
18. Köster W, Stamatis G, Heider A, Avramidis K, Wilke H, et al. (2004) Carboplatin in combination with bendamustine in previously untreated patients with extensive-stage small cell lung cancer (SCLC). Clin Drug Investig 24: 611-618. (Pubitemid 44283969)
19. Layman RM, Ruppert AS, Lynn M, Mrozek E, Ramaswamy B, et al. (2013) Severe and prolonged lymphopenia observed in patients treated with bendamustine and erlotinib for metastatic triple negative breast cancer. Cancer Chemother Pharmacol 71: 1183-1190.
20. Chow KU, Boehrer S, Geduldig K, Krapohl A, Hoelzer D, et al. (2001) In vitro induction of apoptosis of neoplastic cells in low-grade non-Hodgkin's lymphomas using combinations of established cytotoxic drugs with bendamustine. Haematologica 86: 485-493. (Pubitemid 33638976)
21. Chow KU, Noval D, Boehrer S, Ruthardt M, Knau A, et al. (2003) Synergistic effects of chemotherapeutic drugs in lymphoma cells are associated with downregulation of inhibitor of apoptosis proteins (IAPs), prostate-apoptosis-response-gene 4 (Par-4), death-associated protein (Daxx) and with enforced caspase activation. Biochem Pharmacol 66: 711-724. (Pubitemid 37011409)
22. Castegnaro S, Visco C, Chieregato K, Bernardi M, Albiero E, et al. (2012) Cytosine arabinoside potentiates the apoptotic effect of bendamustine on several B- and T-cell leukemia/lymphoma cells and cell lines. Leuk Lymphoma 53: 2262-2258.
23. Visco C, Castegnaro S, Chieregato K, Bernardi M, Albiero E, et al. (2012) The cytotoxic effects of bendamustine in combination with cytarabine in mantle lymphoma cell lines. Blood Cell Mol Dis 48: 68-75.
24. Cai B, Lyu H, Huang J, Wang S, Lee CK, et al. (2013) Combination of bendamustine and entinostat synergistically inhibits proliferation of multiple myeloma cells via induction of apoptosis and DNA damage response. Cancer Lett 335: 343-350.
25. Koenigsmann M, Knauf W, Herold M, Pasold R, Müller G, et al. (2004) Fludarabine and bendamustine in refractory and relapsed indolent lymphoma - multicenter phase I/II trial of the East German Society of Hematology and Oncology (OSHO). Leuk Lymphoma 45: 1821-1827. (Pubitemid 39004071)
26. Weide R, Hess G, Köppler H, Heymanns J, Thomalla J, et al. (2007) German Low Grade Lymphoma Study Group: High anti-lymphoma activity of bendamustine/mitoxantrone/rituximab in rituximab pretreated relapsed or refractory indolent lymphomas and mantle cell lymphomas. A multicenter phase II study of the German Low Grade Lymphoma Study Group (GLSG). Leuk Lymphoma 48: 1299-1306. (Pubitemid 47082223)
27. Visco C, Finotto S, Zambello R, Paolini R, Menin A, et al. (2013) Combination of rituximab, bendamustine, and cytarabine for patients with mantle-cell non-Hodgkin lymphoma ineligible for intensive regimens or autologous transplantation. J Clin Oncol 31: 1442-1449.
28. Visco C, Finotto S, Pomponi F, Sartoli R, Laveder F, et al. (2013) The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high-risk patients with chronic lymphocytic leukemia. Am J Hematol 88: 289-293.
29. Abe M, Nozawa Y, Wakasa H, Ohno H, Fukuhara S (1988) Characterization and comparison of two newly established Epstein-Barr virus-negative lymphoma B-cell lines. Surface markers, growth characteristics, cytogenetics, and transplantability. Cancer 61: 483-490. (Pubitemid 18039362)
30. Hiraoka N, Kikuchi J, Koyama D, Wada T, Mori S, et al. (2013) Alkylating agents induce histone H3K18 hyperacetylation and potentiate HDAC inhibitor-mediated global histone acetylation and cytotoxicity in mantle cell lymphoma. Blood Cancer J 3: e169.
31. Furukawa Y, Vu HA, Akutsu M, Odgerel T, Izumi T, et al. (2007) Divergent cytotoxic effects of PKC412 in combination with conventional antileukemic agents in FLT3 mutation-positive versus -negative leukemia cell lines. Leukemia 21: 1005-1014. (Pubitemid 46672078)
32. Koyama D, Kikuchi J, Hiraoka N, Wada T, Kurosawa H, et al. (2014) Proteasome inhibitors exert cytotoxicity and increase chemosensitivity via transcriptional repression of Notch1 in T-cell acute lymphoblastic leukemia. Leukemia, advanced online publication, 17 January 2014; doi:10.1038/leu.2013. 366.
33. Wright AMP, Gati WP, Paterson ARP (2000) Enhancement of retention and cytotoxicity of 2-chlorodeoxyadenosine in cultured human leukemic lymphoblasts by nitrobenzylthioinosine, an inhibitor of equilibrative nucleoside transport. Leukemia 14: 52-60. (Pubitemid 30068373)
34. Kikuchi J, Yamada S, Koyama D, Wada T, Nobuyoshi M, et al. (2013) The novel orally active proteasome inhibitor K-7174 exerts anti-myeloma activity in vitro and in vivo by down-regulating the expression of class I histone deacetylases. J Biol Chem 288: 25593-25602.
35. Yamauchi T, Negoro E, Kishi S, Takagi K, Yoshida A, et al. (2009) Intracellular cytarabine triphosphate production correlates to deoxycytidine kinase/cytosolic 59-nucleotidase II expression ratio in primary acute myeloid leukemia cells. Biochem Pharmacol 77: 1780-1786.
36. Yamauchi T, Ueda T (2005) A sensitive new method for clinically monitoring cytarabine concentrations at the DNA level in leukemia cells. Biochem Pharmacol 69: 1795-1803. (Pubitemid 40780079)
37. Yamauchi T, Ueda T, Nakamura T (1996) A new sensitive method for determination of intracellular 1-β-D-arabinofuranosylcytosine 59-triphosphate content in human materials in vivo. Cancer Res 56: 1800-1804.
38. Rasschaert M, Schrijvers D, Van den Brande J, Dyck J, Bosmans J, et al. (2007) A phase I study of bendamustine hydrochloride administered day 1+2 every 3 weeks in patients with solid tumours. Br J Cancer 96: 1692-1698. (Pubitemid 46847200)
39. Ogura M, Uchida T, Taniwaki M, Ando K, Watanabe T, et al. (2010) Phase I and pharmacokinetic study of bendamustine hydrochloride in relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma. Cancer Sci 101: 2054-2058.
40. Hill BT (1972) Studies on the transport and cellular distribution of chlorambucil in the Yoshida ascites sarcoma. Biochem Pharmacol 21: 495-502.
41. 31P nuclear magnetic resonance spectroscopic observation of the intracellular transformations of oncostatic cyclophosphamide metabolites. J Med Chem 29: 1206-1210.
42. Pastor-Anglada M, Molina-Arcas M, Casado FJ, Bellosillo B, Colomer D, et al. (2004) Nucleoside transporters in chronic lymphocytic leukemia. Leukemia 18: 385-393. (Pubitemid 38425849)
43. Fernandez-Calotti PX, Colomer D, Pastor-Anglada M (2011) Translocation of nucleoside analogs across the plasma membrane in hematologic malignancies. Nucleosides, Nucleotides and Nucleic Acids 30: 1324-1340.
44. Staib P, Schinköthe T, Dimski T, Lathan B, Boos J, et al. (1999) In-vitro modulation of Ara-CTP accumulation in fresh AML cells by bendamustine in comparison with fludarabine, 2-CDA and gemcitabine. Blood 94: 63a.
45. Gandhi V, Estey E, Keating MJ, Chucrallah A, Plunkett W (1996) Chlorodeoxyadenosine and arbinosylcytosine in patients with acute myelogenous leukemia: Pharmacokinetic, pharmacodynamic, and molecular interactions. Blood 87: 256-264. (Pubitemid 26011840)
46. Chow KU, Boehrer S, Napieralski S, Novak D, Knau A, et al. (2003) In AML cell lines Ara-C combined with purine analogues is able to exert synergistic as well as antagonistic effects on proliferation, apoptosis and disruption of mitochondrial membrane potential. Leuk Lymphoma 44: 165-173. (Pubitemid 36113846)
47. Petersen AJ, Brown RD, Gibson J, Pope B, Luo XF, et al. (1996) Nucleoside transporters, bcl-2 and apoptosis in CLL cells exposed to nucleoside analogues in vitro . Eur J Haematol 56: 213-220. (Pubitemid 26156658)
48. Chan KK, Hong PS, Tutsch K, Trump DL (1994) Clinical pharmacokinetics of cyclophosphamide and metabolites with and without SR-2508. Cancer Res 54: 6421-6429.
49. Herold M, Schulze A, Niederwieser D, Franke A, Fricke HJ, et al. (2006) Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide, vincristine and prednisone (COP) in advanced indolent non-Hodgkin's lymphoma and mantle cell lymphoma: results of a randomised phase III trial (OSHO# 19). J Cancer Res Clin Oncol 132: 105-112.
50. Visani G, Malerba L, Stefani PM, Capria S, Galieni P, et al. (2011) BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients. Blood 118: 3419-3425.