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M, B., M, H.-E., & Z, M. (2018). Effects of Enoxaparin Emulsion on Dimethylbenzanthracene-induced Breast Cancer in Female Rats. Research in Molecular Medicine (RMM), 5(4), 23–30. https://doi.org/10.18502/rmm.v5i4.3062
https://doi.org/10.18502/rmm.v5i4.3062
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Bolandpayeh M
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Hassanpour-Ezzati M
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Mousavi Z
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Published Date
- Oct 10, 2018
Effects of Enoxaparin Emulsion on Dimethylbenzanthracene-induced Breast Cancer in Female Rats
Abstract
Introduction: Enoxaparin is an anticoagulant medication. Anticoagulation inhibits tumor cell-mediated release of angiogenic proteins and diminishes angiogenic response. Angiogenesis is an important event in various cancers such as breast cancer. Angiogenesis provide oxygen and nutrients to tumor cells and causes tumor progression. The aim of the present study was to evaluate the anti-angiogenesis effect of an enoxaparin cream on breast cancer induced by dimethylbenzanthracene in rats.
Methods: In this experimental in vivo study, 50 Wistar female rats were divided into negative control (vehicle), positive control (cream base), and 3 groups with enoxaparin treatment (40, 60, and 80 mg/ml). After one month of treatment along with breast cancer induction by dimethylbenzanthracene, breast tissue samples were isolated and stained with hematoxylin-eosin, and tumor growth suppression rate was calculated. Tumor size (length and width) was measured using a clipper, and the tumor volume was calculated using the following formula: V = (L × W × W)/2, where V is tumor volume, W is tumor width, L is tumor length. The data were analyzed using one-way ANOVA and Tukey’s post hoc test.
Results: Tumor suppression was significantly increased in enoxaparin treatment groups compared to the positive control group (40 mg/ml of enoxaparin treated versus positive control group; P = 0.017, 60 mg/ml of enoxaparin treated versus positive control; P = 0.015, 40 mg/ml of enoxaparin treated versus positive control; P = 0.009, 60 mg/ml of enoxaparin treated versus 40 mg/ml of enoxaparin treated; P = 0.019, and 80 mg/ml of enoxaparin treated versus 40 mg/ml of enoxaparin treated; P = 0.011 in a dose-dependent manner.
Conclusion: Enoxaparin inhibits breast cancer in a dose-dependent manner. The application of enoxaparin cream in patients with breast cancer may considerably reduce tumor growth.
References
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[30] Rousseau A, Van Dreden P, Mbemba E, Elalamy I, Larsen A, Gerotziafas GT. Cancer cells BXPC3 and MCF7
differentially reverse the inhibition of thrombin generation by apixaban, fondaparinux and enoxaparin.
Thromb Res. 2015;136(6):1273-9.
[31] Alam F, Al-Hilal TA, Park J, Choi JU, Mahmud F, Jeong J-H, et al. Multi-stage inhibition in breast cancer metastasis by orally active triple conjugate, LHTD4 (low molecular weight heparin-taurocholatetetrameric deoxycholate). Biomaterials. 2016;86:56-67.
[32] Lei L, Chen Z, Wang Z, Zheng L, Zheng Y, Wang X, et al. Breast liposarcoma with solitary metastasis to the pleura: A case report. Medicine. 2017;96(27).
[33] Shakeri J, Golshani S, Jalilian E, Farnia V, Nooripour R, Alikhani M, et al. Studying the amount of depression and its role in predicting the quality of life of women with breast cancer. Asian Pacific Journal of Cancer Prevention: APJCP. 2016;17(2):643-6.
[34] Rafiemanesh H, Rajaei-Behbahani N, Khani Y, Hosseini S. Incidence trend and epidemiology of common cancers in the center of Iran. Global Journal of Health Science. 2016;8(3):146.
[35] Iorns E, Drews-Elger K, Ward TM, Dean S, Clarke J, Berry D, et al. A new mouse model for the study of human breast cancer metastasis. PloS One. 2012;7(10):e47995.
[36] Vandersluis AD, Venier NA, Colquhoun AJ, Sugar L, Pollak M, Kiss A, et al. Exercise does not counteract the effects of a “westernized” diet on prostate cancer xenografts. The Prostate. 2013;73(11):1223-32.
[37] Djaafar S, Dunand-Sautier I, Gonelle-Gispert C, Lacotte S, De Agostini A, Petro M, et al. Enoxaparin attenuates mouse colon cancer liver metastases by inhibiting heparanase and interferon-γ-inducible chemokines. Anticancer Res. 2016;36(8):4019-32.
[38] T Gerotziafas G, Galea V, Mbemba E, Sassi M, Roman M-P, Khaterchi A, et al. Effect of low molecular weight heparins and fondaparinux upon thrombin generation triggered by human pancreatic cancer cells BXPC3. Curr Vasc Pharmacol. 2014;12(6):893-902.
[39] Mousa SA. Low−molecular−weight heparins in thrombosis and cancer: emerging links. Cardiovasc Ther. 2004;22(2):121-34.
[40] Mousa SA, Mohamed S. Anti-angiogenic mechanisms and efficacy of the low molecular weight heparin, tinzaparin: anti-cancer efficacy. Oncol Rep. 2004;12(4):683-8.
[41] Zhang N, Lou W, Ji F, Qiu L, Tsang BK, Di W. Low molecular weight heparin and cancer survival: clinical trials and experimental mechanisms. J Cancer Research Clin Oncol. 2016;142(8):1807-16.
of literature. Thromb Res. 2013;132(4):487-9.
[2] Scotté F, Rey J, Launay-Vacher V. Thrombosis, cancer and renal insufficiency: low molecular weight heparin at the crossroads. Support Care Cancer. 2012;20(12):3033-42.
[3] Welti J, Loges S, Dimmeler S, Carmeliet P. Recent molecular discoveries in angiogenesis and antiangiogenic therapies in cancer. J Clin Invest. 2013;123(8):3190-200.
[4] Dimova I, Popivanov G, Djonov V. Angiogenesis in cancer-general pathways and their therapeutic implications. Jbuon. 2014;19(1):15-21.
[5] Tichy JR, Lim E, Anders CK. Breast cancer in adolescents and young adults: a review with a focus on biology. Journal of the National Comprehensive Cancer Network. 2013;11(9):1060-9.
[6] Kozłowski J, Kozłowska A, Kocki J. Breast cancer metastasis-insight into selected molecular mechanisms of the phenomenon. Advances in Hygiene & Experimental Medicine/Postepy Higieny i Medycyny Doswiadczalnej. 2015;69.
[7] Charalel RA, Vedantham S, editors. Venous Disease: Deep Vein Thrombosis Interventions in Cancer Patients. Seminars in interventional radiology; 2017: Thieme Medical Publishers.
[8] Fei X, Wang H, Yuan W, Wo M, Jiang L. Tissue factor pathway inhibitor-1 is a valuable marker for the
prediction of deep venous thrombosis and tumor metastasis in patients with lung cancer. BioMed Research International. 2017;2017.
[9] Siegal D, Garcia D. Anticoagulants in cancer. Journal of Thrombosis and Haemostasis. 2012;10(11):2230-
41.
[10] Gary T. Cancer related venous thromboembolism–prophylaxis and therapy. Vasa. 2014;43(4):245-51.
[11] Rey S, Schito L, Wouters BG, Eliasof S, Kerbel RS. Targeting hypoxia-inducible factors for antiangiogenic
cancer therapy. Trends in Cancer. 2017;3(7):529-41.
[12] Shanmugam MK, Warrier S, Kumar AP, Sethi G, Arfuso F. Potential role of natural compounds as antiangiogenic agents in cancer. Curr Vasc Pharmacol. 2017;15:503-19.
[13] Luvero D, Plotti F, Lopez S, Scaletta G, Capriglione S, Montera R, et al. Antiangiogenics and immunotherapies in cervical cancer: an update and future’s view. Med Oncol. 2017;34(6):115.
[14] Retamales-Ortega R, Oróstica L, Vera C, Cuevas P, Hernández A, Hurtado I, et al. Role of nerve growth
factor (NGF) and miRNAs in epithelial ovarian cancer. International Journal of Molecular Sciences. 2017;18(3):507.
[15] Cimpean AM, Tamma R, Ruggieri S, Nico B, Toma A, Ribatti D. Mast cells in breast cancer angiogenesis. Critical Reviews in Oncology/Hematology. 2017;115:23-6.
[16] Barron GA, Goua M, Wahle KW, Bermano G. Circulating levels of angiogenesis-related growth factors in breast cancer: A study to profile proteins responsible for tubule formation. Oncol Rep. 2017;38(3):1886-94.
[17] Ferroni P, Roselli M, Portarena I, Formica V, Riondino S, La Farina F, et al. Plasma plasminogen activator inhibitor-1 (PAI-1) levels in breast cancer–relationship with clinical outcome. Anticancer Res. 2014;34(3):1153-61.
[18] Ferreira JG, Diniz PMM, De Paula CAA, Lobo YA, Paredes-Gamero EJ, Paschoalin T, et al. The impaired viability of prostate cancer cell lines by the recombinant plant kallikrein inhibitor. J BiolChem. 2013;288(19):13641-54.
[19] Poupard N, Badarou P, Fasani F, Groult H, Bridiau N, Sannier F, et al. Assessment of HeparanaseMediated Angiogenesis Using Microvascular Endothelial Cells: Identification of λ-Carrageenan Derivative as a Potent Anti Angiogenic Agent. Mar Drugs. 2017;15(5):134.
[20] Quade M, Knaack S, Weber D, König U, Paul B, Simon P, et al. Heparin modification of a biomimetic bone matrix modulates osteogenic and angiogenic cell response in vitro. Eur Cell Mater. 2017;33:105.
[21] Cheng W, Dahmani FZ, Zhang J, Xiong H, Wu Y, Yin L, et al. Anti-angiogenic activity and antitumor efficacy of amphiphilic twin drug from ursolic acid and low molecular weight heparin. Nanotechnology. 2017;28(7):075102.
[22] Elit LM, Lee AY, Parpia S, Swystun LL, Liaw PC, Hoskins P, et al. Dalteparin low molecular weight heparin (LMWH) in ovarian cancer: a phase II randomized study. Thromb Res. 2012;130(6):894-900.
[23] Marchetti M, Vignoli A, Russo L, Balducci D, Pagnoncelli M, Barbui T, et al. Endothelial capillary tube formation and cell proliferation induced by tumor cells are affected by low molecular weight heparins and unfractionated heparin. Thromb Res. 2008;121(5):637-45.
[24] von Tempelhoff G-F, Harenberg J, Niemann F, Hommel G, Kirkpatrick CJ, Heilmann L. Effect of low molecular weight heparin (Certoparin) versus unfractionated heparin on cancer survival following breast and pelvic cancer surgery: A prospective randomized double-blind trial. Int J Oncol. 2000;16(4):815-39.
[25] Yin W, Zhang J, Jiang Y, Juan S. Combination therapy with low molecular weight heparin and Adriamycin results in decreased breast cancer cell metastasis in C3H mice. Experimental and Therapeutic Medicine. 2014;8(4):1213-8.
[26] Kang J, Hennessy-Strahs S, Kwiatkowski P, Bermudez CA, Acker MA, Atluri P, et al. Continuous-flow LVAD support causes a distinct form of intestinal angiodysplasia novelty and significance. Circ Res. 2017;121(8):963-9.
[27] Alfer J, Happel L, Dittrich R, Beckmann MW, Hartmann A, Gaumann A, et al. Insufficient angiogenesis: cause of abnormally thin endometrium in subfertile patients? Geburtshilfe und Frauenheilkunde. 2017;77(07):756-64.
[28] Duh EJ, Sun JK, Stitt AW. Diabetic retinopathy: current understanding, mechanisms, and treatment strategies. JCI insight. 2017;2(14).
[29] Garona J, Pifano M, Scursoni AM, Gomez DE, Alonso DF, Ripoll GV. Insight into the effect of the vasopressin analog desmopressin on lung colonization by mammary carcinoma cells in BALB/c mice. Anticancer Res. 2014;34(9):4761-5.
[30] Rousseau A, Van Dreden P, Mbemba E, Elalamy I, Larsen A, Gerotziafas GT. Cancer cells BXPC3 and MCF7
differentially reverse the inhibition of thrombin generation by apixaban, fondaparinux and enoxaparin.
Thromb Res. 2015;136(6):1273-9.
[31] Alam F, Al-Hilal TA, Park J, Choi JU, Mahmud F, Jeong J-H, et al. Multi-stage inhibition in breast cancer metastasis by orally active triple conjugate, LHTD4 (low molecular weight heparin-taurocholatetetrameric deoxycholate). Biomaterials. 2016;86:56-67.
[32] Lei L, Chen Z, Wang Z, Zheng L, Zheng Y, Wang X, et al. Breast liposarcoma with solitary metastasis to the pleura: A case report. Medicine. 2017;96(27).
[33] Shakeri J, Golshani S, Jalilian E, Farnia V, Nooripour R, Alikhani M, et al. Studying the amount of depression and its role in predicting the quality of life of women with breast cancer. Asian Pacific Journal of Cancer Prevention: APJCP. 2016;17(2):643-6.
[34] Rafiemanesh H, Rajaei-Behbahani N, Khani Y, Hosseini S. Incidence trend and epidemiology of common cancers in the center of Iran. Global Journal of Health Science. 2016;8(3):146.
[35] Iorns E, Drews-Elger K, Ward TM, Dean S, Clarke J, Berry D, et al. A new mouse model for the study of human breast cancer metastasis. PloS One. 2012;7(10):e47995.
[36] Vandersluis AD, Venier NA, Colquhoun AJ, Sugar L, Pollak M, Kiss A, et al. Exercise does not counteract the effects of a “westernized” diet on prostate cancer xenografts. The Prostate. 2013;73(11):1223-32.
[37] Djaafar S, Dunand-Sautier I, Gonelle-Gispert C, Lacotte S, De Agostini A, Petro M, et al. Enoxaparin attenuates mouse colon cancer liver metastases by inhibiting heparanase and interferon-γ-inducible chemokines. Anticancer Res. 2016;36(8):4019-32.
[38] T Gerotziafas G, Galea V, Mbemba E, Sassi M, Roman M-P, Khaterchi A, et al. Effect of low molecular weight heparins and fondaparinux upon thrombin generation triggered by human pancreatic cancer cells BXPC3. Curr Vasc Pharmacol. 2014;12(6):893-902.
[39] Mousa SA. Low−molecular−weight heparins in thrombosis and cancer: emerging links. Cardiovasc Ther. 2004;22(2):121-34.
[40] Mousa SA, Mohamed S. Anti-angiogenic mechanisms and efficacy of the low molecular weight heparin, tinzaparin: anti-cancer efficacy. Oncol Rep. 2004;12(4):683-8.
[41] Zhang N, Lou W, Ji F, Qiu L, Tsang BK, Di W. Low molecular weight heparin and cancer survival: clinical trials and experimental mechanisms. J Cancer Research Clin Oncol. 2016;142(8):1807-16.