Browse > Article
http://dx.doi.org/10.5483/BMBRep.2017.50.8.099

Neuropeptide Y improves cisplatin-induced bone marrow dysfunction without blocking chemotherapeutic efficacy in a cancer mouse model  

Park, Min Hee (Stem Cell Neuroplasticity Research Group, Kyungpook National University)
Jung, In Kyung (Stem Cell Neuroplasticity Research Group, Kyungpook National University)
Min, Woo-Kie (Department of Orthopaedic Surgery, Kyungpook National University Hospital)
Choi, Jin Ho (Department of Mechanical Engineering, Gumi University)
Kim, Gyu Man (School of Mechanical Engineering, Kyungpook National University)
Jin, Hee Kyung (Stem Cell Neuroplasticity Research Group, Kyungpook National University)
Bae, Jae-sung (Stem Cell Neuroplasticity Research Group, Kyungpook National University)
Publication Information
BMB Reports / v.50, no.8, 2017 , pp. 417-422 More about this Journal
Abstract
Cisplatin is the most effective and widely used chemotherapeutic agent for many types of cancer. Unfortunately, its clinical use is limited by its adverse effects, notably bone marrow suppression leading to abnormal hematopoiesis. We previously revealed that neuropeptide Y (NPY) is responsible for the maintenance of hematopoietic stem cell (HSC) function by protecting the sympathetic nervous system (SNS) fibers survival from chemotherapy-induced bone marrow impairment. Here, we show the NPY-mediated protective effect against bone marrow dysfunction due to cisplatin in an ovarian cancer mouse model. During chemotherapy, NPY mitigates reduction in HSC abundance and destruction of SNS fibers in the bone marrow without blocking the anticancer efficacy of cisplatin, and it results in the restoration of blood cells and amelioration of sensory neuropathy. Therefore, these results suggest that NPY can be used as a potentially effective agent to improve bone marrow dysfunction during cisplatin-based cancer therapy.
Keywords
Bone marrow dysfunction; Cancer; Chemotherapy-induced side effects; Hematopoietic stem cell; Neuropeptide Y;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Aloe L, Manni L, Properzi F, De Santis S and Fiore M (2000) Evidence that nerve growth factor promotes the recovery of peripheral neuropathy induced in mice by cisplatin: behavioral, structural and biochemical analysis. Auton Neurosci 86, 84-93   DOI
2 Kawamoto T (2003) Use of a new adhesive film for the preparation of multipurpose fresh-frozen sections from hard tissues, whole-animals, insects and plants. Arch Histol Cytol 66, 123-143   DOI
3 Blanchard EM (2012) Cisplatin and solid tumours: still working, after all these years. J Solid Tumors 2, 26-33
4 Siddik ZH (2003) Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 22, 7265-7279   DOI
5 Wang D and Lippard SJ (2005) Cellular processing of platinum anticancer drugs. Nat Rev Drug Discov 4, 307-320   DOI
6 Cepeda V, Fuertes MA, Castilla J, Alonso C, Queve-do C and Perez JM (2007) Biochemical mechanisms of cisplatin cytotoxicity. Anticancer Agents Med Chem 7, 3-18   DOI
7 Einhorn LH (2002) Curing metastatic testicular cancer. Proc Natl Acad Sci U S A 99, 4592-4595   DOI
8 Cullen KJ, Yang Z, Schumaker L and Guo Z (2007) Mitochondria as a critical target of the chemotheraputic agent cisplatin in head and neck cancer. J Bioenerg Biomembr 39, 43-50   DOI
9 Armstrong DK, Bookman MA, McGuire W, Bristow RE, Schilder JM and Group GO (2007) A phase I study of paclitaxel, topotecan, cisplatin and filgrastim in patients with newly diagnosed advanced ovarian epithelial malignancies: a Gynecologic Oncology Group study. Gynecol Oncol 105, 667-671   DOI
10 Ridwelski K, Gebauer T, Fahlke J et al (2001) Combination chemotherapy with docetaxel and cisplatin for locally advanced and metastatic gastric cancer. Ann Oncol 12, 47-51
11 Niell HB, Herndon JE, Miller AA et al (2005) Randomized phase III intergroup trial of etoposide and cisplatin with or without paclitaxel and granulocyte colony-stimulating factor in patients with extensive-stage small-cell lung cancer: Cancer and Leukemia Group B Trial 9732. J Clin Oncol 23, 3752-3759   DOI
12 Chaudhry V, Rowinsky EK, Sartorius SE, Donehower RC and Cornblath DR (1994) Peripheral neuropathy from taxol and cisplatin combination chemotherapy: clinical and electrophysiological studies. Ann Neurol 35, 304-311   DOI
13 Zukowska-Grojec Z (1995) Neuropeptide Y. A novel sympathetic stress hormone and more. Ann NY Acad Sci 771, 219-233   DOI
14 Pabla N, Dong G, Jiang M et al (2011) Inhibition of $PKC{\delta}$ reduces cisplatin-induced nephrotoxicity without blocking chemotherapeutic efficacy in mouse models of cancer. J Clin Invest 121, 2709-2722   DOI
15 Hatzopoulos S, Di Stefano M, Albertin A and Martini A (1999) Evaluation of cisplatin ototoxicity in a rat animal model. Ann NY Acad Sci 884, 211-225   DOI
16 Noach EJ, Ausema A, van Os R et al (2000) Chemotherapy prior to autologous bone marrow transplantation impairs long-term engraftment in mice. Exp Hematol 28, 1325-1333   DOI
17 Banfi A, Podesta M, Fazzuoli L et al (2001) High-dose chemotherapy shows a dose-dependent toxicity to bone marrow osteoprogenitors: a mechanism for post-bone marrow transplantation osteopenia. Cancer 92, 2419-2428   DOI
18 Lucas D, Scheiermann C, Chow A et al (2013) Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration. Nat Med 19, 695-703   DOI
19 Kalra SP and Kalra PS (2004) NPY and cohorts in regulation appetite, obesity and metabolic syndrome: beneficial effects of gene therapy. Neuropeptides 38, 201-211   DOI
20 Kuo LE, Kitlinska JB, Tilan JU et al (2007) Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome. Nat Med 13, 803-811   DOI
21 Santos-Carvalho A, Elvas F, Alvaro AR, Ambrosio AF and Cavadas C (2013) Neuropeptide Y receptors activation protects rat retinal neural cells against necrotic and apoptotic cell death induced by glutamate. Cell Death Dis 4, e636   DOI
22 Perseghin P, Terruzzi E, Dassi M et al (2009) Management of poor peripheral blood stem cell mobilization: incidence, predictive factors, alternative strategies and outcome. A retrospective analysis on 2177 patients from three major Italian institutions. Transfus Apher Sci 41, 33-37   DOI
23 Park MH, Jin HK, Min WK et al (2015) Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow. EMBO J 34, 1648-1660   DOI
24 Park MH, Min WK, Jin HK and Bae JS (2015) Role of neuropeptide Y in the bone marrow hematopoietic stem cell microenvironment. BMB Rep 48, 645-646   DOI
25 Can A (2008) Haematopoietic stem cells niches: Interrelations between structure and function. Transfus Apher Sci 38, 261-268   DOI
26 Butler JM, Nolan DJ, Vertes EL et al (2010) Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells. Cell Stem Cell 6, 251-264   DOI
27 Robinson SN, Freedman AS, Neuberg DS, Nadler LM and Mauch PM (2000) Loss of marrow reserve from dose-intensified chemotherapy results in impaired hematopoietic reconstitution after autologous transplantation: CD34+, CD34+38- and week-6 CAFC assays predict poor engraftment. Exp Hematol 28, 1325-1333   DOI
28 Park MH, Lee JK, Kim N et al (2016) Neuropeptide Y Induces Hematopoietic Stem/Progenitor Cell Mobilization by Regulating Matrix Metalloproteinase-9 Activity through Y1 Receptor in Osteoblasts. Stem Cells 34, 2145-2156   DOI
29 Kim N, Min WK, Park MH, Lee JK, Jin HK and Bae JS (2016) Neuropeptide Y protects kidney against cisplatininduced nephrotoxicity by regulating p53-dependent apoptosis pathway. BMB Rep 49, 288-292.   DOI