Beyond anticoagulant: Heparin as a potential anti-cancer agent

Authors

  • Ravi Lokwani Faculty of Industrial Sciences and Technology, University Malaysia Pahang, 26300 Gambang, Pahang, Malaysia.
  • Nina Suhaity Azmi Faculty of Industrial Sciences and Technology, University Malaysia Pahang, 26300 Gambang, Pahang, Malaysia.
  • Mashitah Mohd Yusoff Faculty of Industrial Sciences and Technology, University Malaysia Pahang, 26300 Gambang, Pahang, Malaysia.
  • Solachuddin Jauhari Arief Ichwan Human Molecular & Cellular Biology Research Cluster (iMoleC), ICRACU-International Islamic University Malaysia, Kuantan Campus, Jalan Sultan Ahmad Shah, Bandar Indera Mahkota, Kuantan, 25200, Pahang, Malaysia

DOI:

https://doi.org/10.54987/jobimb.v2i2.160

Abstract

Heparin has been in the market since the last six decades due to its potential anticoagulant property. The mechanism of its anti-coagulation effect is well established. Along with its anticoagulant activity the other activity that is gathering a lot of importance now-a-days is its ability to arrest the progression of tumors specially some solid forms of tumors such as small cell lung carcinoma and pancreatic tumors. The chemically modified and light molecular weight fractions of heparin have been found to be more active in countering tumor progression. In this review we discuss a brief history of this versatile biomolecule with its clinical data and postulated mechanism of action as per recent studies. This review also highlighted the approach of heparin-conjugated nanoparticles to achieve targeted drug delivery with synergistic response in tumor cells.

References

Wardrop D, Keeling D. The story of the discovery of heparin and warfarin. Br J Haem. 2008; 141(6):757–763.

Nader HB, Chavante SF, Oliveira FW, Medeiros GF, Leite EL, Toma L, Tersariol ILS, Porcionatto MA, Dietrich CP. Heparan sulfates and heparins: similar compounds performing the same functions in vertebrates and invertebrates? Braz J Med Biol Res. 1999; 32:529-538.

Warda M, Mao W, Toida T, Linhardt RJ. Turkey intestine as a commercial source of heparin? Comparative structural studies of intestinal avian and mammalian glycosaminoglycans. Comp Biochem Physiol B Biochem Mol Biol. 2003; 134(1):189–97.

Ototani N, Kikuchi M, Yosizawa Z. Comparative studies on the structures of highly active and relatively inactive forms of whale heparin. J Biochem. 1981; 90:241–246.

Warda M, Gouda E M, Toida T, Chi L, Linhardt RJ. Isolation and characterization of raw heparin from dromedary intestine: evaluation of a new source of pharmaceutical heparin. Comp Biochem Physiol C Toxicol Pharmacol. 2003; 136:357– 365.

Bland CE, Ginsburg H, Silbert JE, Metcalfe DD. Mouse heparin proteoglycan Synthesis by mast cell fibroblast monolayers during lymphocyte dependent mast cell proliferation. J Biol Chem. 1982; 257:8661–8666.

Linhardt RJ, Ampofo SA, Fareed J, Hoppensteadt D, Folkman J, Mulliken JB. Isolation and characterization of human heparin. Biochemistry. 1992; 31: 12441–12445.

Hovingh P, Linker A. An unusual heparan sulfate isolated from lobsters (Homarus americanus). J Biol Chem. 1982; 257:9840–9844.

Dietrich CP, Paiva JF, Castro RAB, Chavante SF, Jeske W, Fareed J, Gorin, PA, Nadher HB. Structural features and anticoagulant activities of a novel natural low-molecular-weight heparin from the shrimp Penaeus brasiliensis. Biochim Biophys Acta. 1999; 1428: 273–283.

Hovingh P, Linker A. Glycosaminoglycans in Anodonta californiensis, a freshwater mussel. Biol Bull. 1993;185:263–276.

Pejler G, Danielsson A, Bjork I, Lindahl U, Nader HB, Dietrich CP. Structure and antithrombin-binding properties of heparin isolated from the clams Anomalocardia brasiliana and Tivela mactroides. J Biol Chem. 1987; 262:11413–11421.

Medeiros GF, Mendes A, Castro RAB, Baffl EC, Nader HB, Dietrich CP. Distribution of sulfated glycosaminoglycans in the animal kingdom: widespread occurrence of heparin like compounds in invertebrates. Biochim Biophys Acta. 2000; 1475:287– 294.

Azmi NS, Fernig DG. Heparan sulfate surfaces to probe the functions of the master regulator of the extracellular spaces. Handbook of Biofunctional Surfaces. Pan Standford Publishing. Wolfgang Knoll. 16: 2013; 591-609.

Chavante SF, Brito, AS, Lima M, Yates E, Nader H, Guerrini M, Torri G, Bisio A. A heparin-like glycosaminoglycan from shrimp containing high levels of 3-O-sulfated D-glucosamine groups in an unusual trisaccharide sequence. Carbohydr Res. 2014; 390: 59–66.

Petitou M, Duchaussoy P, Driguez PA, Jaurand G, Herault JP, Lormeau JC, Boeckel CAV, Herbert JM. First synthetic carbohydrates with the full antocoagulant properties of heparin. Angew Chem Int Ed Engl. 1998; 37: 3009–3014.

Liang Y, Kiick KL. Heparin-functionalized polymeric biomaterials in tissue engineering and drug delivery applications. Acta Biomaterialia. 2014; 10(4):1588–1600.

Li Y, Luo JY, Cui HF, Zheng L, Du SS. Study on anti-metastasis of heparin derivatives as ligand antagonist of P-selectin. Biomed Pharmacother. 2010; 64(10): 654–658.

Zacharski LR, Lee AY. Heparin as an anticancer therapeutic. Expert Opin Investig Drugs. 2008; 17(7):1029-1037.

Nash GF, Walsh DC, Kakkar AK. The role of the coagulation system in tumour angiogenesis. Lancet Oncol. 2001; 2:608-613.

Ruf W, Disse J, Carneiro-Lobo TC, Yokota N, Schaffner F. Tissue factor and cell signalling in cancer progression and thrombosis. J Thromb Haemost. 2011; 9(1): 306-15.

Yip GW, Smollich M, Gotte M. Therapeutic value of glycosaminoglycans in cancer. Mol Cancer Ther. 2006; 5:2139–2148.

Drago JR, Weed P, Fralisch A. The evaluation of heparin in control of metastasis of Nb rat androgen-insensitive prostate carcinoma. Anticancer Res. 1984; 4:171–182.

Pross M, Lippert H, Misselwitz F, Nestler G, Kruger S, Langer H, Halangk W, Schulz HU. Low-molecular-weight heparin (reviparin) diminishes tumor cell adhesion and invasion in vitro, and decreases intraperitoneal growth of colonadeno-carcinoma cells in rats after laparoscopy. Thromb Res. 2003; 110(4), 215–220.

Amirkhosravi A, Mousa S A, Amaya M, Francis J L. Anti-metastatic effect of tinzaparin, a low-molecular-weight heparin. Journal Thromb Haemost. 2003; 1(9):1972-1976.

Sciumbata T, Caretto P, Pirovano P, Pozzi P, Cremonesi P, Galimberti G, Leoni F, Marcucci F. Treatment with modified heparins inhibits experimental metastasis formation and leads, in some animals, to long-term survival. Invas Metas. 1996; 16(3):132-143.

Elit LM, Lee AY, Parpia S, Swystun LL, Liaw PC, Hoskins P, Julian DH, Julian JA, Levine MN. Dalteparin low-molecular-weight heparin (LMWH) in ovarian cancer: a phase II randomized study. Thromb Res. 2012; 130(6): 894–900.

Albert-Weil J, Nehorias J. Two cases of neoplasms not justified for classical therapy, treated with intravenous injections of heparin and intramuscular injections of leech extracts. Pathol Gen Physiol Clin. 1954; 54:1014-1020.

Lebeau B, Chastang C, Brechot JM, Capron F, Dautzenberg B, Delaisements C, Mormet M, Brun J, Hurdebourcq JP, Lemarie E. Subcutaneous heparin treatment increases survival in small cell lung cancer. “Petites Cellules†Group. Cancer. 1994; 74:38-45.

Green D, Hull RD, Brant R, Pineo GF. Lower mortality in cancer patients treated with low-molecular-weight versus standard heparin. Lancet. 1992; 339:1476.

Gould MK, Dembitzer AD, Doyle RL, Hastie TJ, Garber AM. Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials. Ann Intern Med. 1999; 130:800-809.

Kakkar AK, Levine MN, Kadziola Z, Lemoine NR, Low V, Patel HK, Rustin G, Thomas M, Quigley M, Williamson RC. Low-molecular-weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS). J Clin Oncol. 2004; 22:1944-8.

Klerk CP, Smorenburg SM, Otten HM, Lensing AW, Prins MH, Piovella F, Prandoni P, Boss MM, Richel DJ, Tienhoven G, Buller HR. The effect of low-molecular-weight heparin on survival in patients with advanced malignancy. J Clin Oncol. 2005; 23:2130-2135.

Sideras K, Schaefer PL, Okuno SH, Sloan JA, Kutteh L, Fitch TR, Dakhil SR, levitt R, Alberts SR, Morton RF, Rowland KM, Novotny PJ, Loprinzi CL. Low-molecular-weight heparin in patients with advanced cancer: a phase 3 clinical trial. Mayo Clin Proc. 2006; 81:758-767.

Altinbas M, Coskun HS, Er O, Ozkan M, Eser B, Unal A, Cetin M, Soyuer S. A randomized clinical trial of combination chemotherapy with and without low- molecular-weight heparin in small cell lung cancer. J Thromb Haemost. 2004; 2:1266-1271.

Lazo-Langner A, Goss GD, Spaans JN, Rodger MA. The effect of low- molecular-weight heparin on cancer survival. A systematic review and meta-analysis of randomized trials. J Thromb Haemost. 2007; 5:729-737.

Noble S. Heparins and cancer survival: where do we stand? Thromb Res. 2014; 133 (2):133–138.

Borsig L, Wong R, Feramisco J, Nadeau DR, Varki NM, Varki A. Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis. Proc Natl Acad Sci U S A. 2001; 98:3352–3357.

Varki NM, Varki A. Heparin Inhibition of Selectin-Mediated Interactions during the Hematogenous Phase of Carcinoma Metastasis: Rationale for Clinical Studies in Humans. Semin Thromb Hemost. 2002; 28:53–66.

Im JH, Fu W, Wang H, Bhatia SK, Hammer DA, Kowalska MA, Muschel RJ. Coagulation facilitates tumor cell spreading in the pulmonary vasculature during early metastatic colony formation. Cancer Res. 2004; 64:8613–8619

Vlodavsky I, Ilan N, Nadir Y, Brenner B, Katz BZ, Naggi A, Torri G, Casu B, Sasisekharan R. Heparanase, heparin and the coagulation system in cancer progression. Thromb Res. 2007;120 Suppl 2:112–120.

Mousa SA, Petersen LJ. Anti-cancer properties of low-molecular-weight heparin: preclinical evidence. Thromb Haemost. 2009; 102:258–267.

Hostettler N, Naggi A, Torri G, Ishai-Michaaeli R, Casu B, Vlodoavsky l, Borsig L. P-selectin- and heparanase-dependent antimetastatic activity of non-anticoagulant heparins. FASEB J. 2007; 21:3562–3572.

Kragh M, Binderup L, Vig Hjarnaa PJ, Bramm E, Johansen KB, Frimundt Peterson C. Non-anti-coagulant heparin inhibits metastasis but not primary tumor growth. Oncol Rep. 2005;14:99–104.

Yoshitomi Y, Nakanishi H, Kusano Y, Munesue S, Tatematsu M, Yamashina I, Okayama M. Inhibition of experimental lung metastases of Lewis lung carcinoma cells by chemically modified heparin with reduced anticoagulant activity. Cancer Lett. 2004; 207:165–174.

Lapierre F, Holme K, Lam L, Tressier RJ, Storm N, Wee J, Stack RJ, Castellot J, Tyrell DJ. Chemical modifications of heparin that diminish its anticoagulant but preserve its heparanase-inhibitory, angiostatic, anti-tumor and anti- metastatic properties. Glycobiology.1996; 6:355–366.

Borsig L, Wong R, Hynes RO, Varki NM, Varki A. Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis. Proc Natl Acad Sci USA. 2002; 99:2193–2198.

Vlodavsky I, Eldor A, Haimovitz-Friedman A, Matzner Y, Ishai-Michaeli R, Lider O, Naparstek Y, Cohen IR, Fuks Z. Expression of heparanase by platelets and circulating cells of the immune system: possible involvement in diapedesis and extravasation. Invas Meta. 1992; 12:112–127.

Stevenson JL, Choi SH, Varki A. Differential metastasis inhibition by clinically relevant levels of heparins–correlation with selectin inhibition, not antithrombotic activity. Clin Cancer Res. 2005;11: 7003–7011.

Ludwig RJ, Alban S, Bistrian R, Boehncke WH, Kaufimann R, Hensschler R, Gille J. The ability of different forms of heparins to suppress P-selectin function in vitro correlates to their inhibitory capacity on blood borne metastasis in vivo. Thromb Haemost. 2006; 95:535–540.

Nakajima M, Irimura T, Nicolson GL. Heparanases and tumor metastasis. J Cell Biochem. 1988; 36:157–167.

Vlodavsky I, Korner G, Ishai-Michaeli R, Bashkin P, Bar-Shavit R, Fuks Z. Extracellular matrix- resident growth factors and enzymes: possible involvement in tumor metastasis and angiogenesis. Cancer Meta. 1990; 9:203–226.

Vlodavsky I, Goldshmidt O, Zcharia E, Atzmon R, Rangini-Guatta Z, Elkin M, Peretz T, Friedmann Y. Mammalian heparanase: involvement in cancer metastasis, angiogenesis and normal development. Semin Cancer Biol. 2002; 12:121–129.

Maxhimer JB, Quiros RM, Stewart R, Dowalatshahi K, Gattuso P, Fan M, Prinz RA, Xu X Heparanase-1 expression is associated with the metastatic potential of breast cancer. Surgery 2002; 132:326–333.

Friedmann Y, Vlodavsky I, Aingorn H, AvivA, Peretz T, Pecker l, Pappo O. Expression of heparanase in normal, dysplastic, and neoplastic human colonic mucosa and stroma. Evidence for its role in colonic tumorigenesis. Am J Pathol. 2000; 157:1167–1175.

Ginath S, Menczer J, Friedmann Y, Aingorm H, Aviva A, Tajimak, Dantes A, Glezerman M, Vlodavasky I, Amsterdam A. Expression of heparanase, Mdm2, and erbB2 in ovarian cancer. Int J Oncol. 2001; 18:1133–44.

Gohji K, Hirano H, Okamoto M, Kitazawa S. Toyoshima M, Dong J, Katsuoko Y, Nakajima M. Expression of three extracellular matrix degradative enzymes in bladder cancer. Int J Cancer 2001; 95:295–301.

Koliopanos A, Friess H, Kleeff J, Shi X, Liao Q, Pecker I, Vlodovasky I, Zimmermann A, Buchler MW. Heparanase expression in primary and metastatic pancreatic cancer. Cancer Res 2001; 61:4655–4659.

Bitan M, Polliack A, Zecchina G, et al. Heparanase expression in human leukemias is restricted to acute myeloid leukemias. Exp Hematol. 2002; 30:34–41.

Takahashi H, Ebihara S, Okazaki T, Suzuki S, Asada M, Kubo H, Sasaki H. Clinical significance of heparanase activity in primary resected non-small cell lung cancer. Lung Cancer. 2004; 45:207–214.

Yang Y, Macleod V, Bendre M, Huang Y, Thesus AM, MiaoHQ, Kussie P, Yaccoby S, Suva LJ, Kelly T Sanderson RD. Heparanase promotes the spontaneous metastasis of myeloma cells to bone. Blood. 2005; 105:1303–1309.

Ishai-Michaeli R, Eldor A, Vlodavsky I. Heparanase activity expressed by platelets, neutrophils, and lymphoma cells releases active fibroblast growth factor from extracellular matrix. Cell Regul. 1990; 1:833–842.

Whitelock JM, Murdoch AD, IozzoRV, Underwood PA.The degradation of human endothelial cell-derived perlecan and release of bound basic fibroblast growth factor by stromelysin, collagenase, plasmin, and heparanases. J Biol Chem. 1996; 271:10079–10086.

Sanderson RD, Yang Y, Suva LJ, Kelly T. Heparan sulfate proteoglycans and heparanase—partners in osteolytic tumor growth and metastasis. Matrix Biol. 2004; 23:341–52.

Elkin M, Ilan N, Ishai-Michaeli R, Friedman Y, Papo O, Pecker I, Vlodavsky I. Heparanase as mediator of angiogenesis: mode of action. FASEB J. 2001; 15:1661–1663.

Kato M, Wang H, Kainulainen V, Fitzgerals ML, Ledbetter S, Ornitz DM, Bernfield M. Physiological degradation converts the soluble syndecan-1 ectodomain from an inhibitor to a potent activator of FGF-2. Nat Med. 1998; 4:691–697.

Irimura T, Nakajima M, Nicolson GL. Chemically modified heparins as inhibitors of heparan sulfate specific endo-beta-glucuronidase (heparanase) of metastatic melanoma cells. Biochemistry. 1986; 25:5322–5328.

Vlodavsky I, Mohsen M, Lider O, Svahn CM, Ekre HP, Vigoda M, Ishai-Michaeli R, Peretz T. Inhibition of tumor metastasis by heparanase inhibiting species of heparin. Invas Meta. 1994; 14:290–302.

Parish CR, Coombe DR, Jakobsen KB, Bennett FA, Underwood PA. Evidence that sulphated polysaccharides inhibit tumour metastasis by blocking tumour-cell-derived heparanases. Int J Cancer. 1987;40:511–518.

Vlodavsky I, Friedmann Y, Elkin M, Aingorn H, Atzmon R, Ishai-Michaeli R, Bitan M, Pappo O, Peretz T, Michal I, Spector L, Pecker I. Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis. Nat Med. 1999; 5:793–802.

Poggi A, Rossi C, Casella N, Bruno C, Sturiale L, Dossi C, Naggi A. Inhibition of B16-BL6 melanoma lung colonies by semisynthetic sulfaminoheparosan sulfates from E.coli K5 polysaccharide. Semin Thromb Hemost. 2002; 28:383–392.

Miao HQ, Elkin M, Aingorn E, Ishai-Michaeli R, Stein CA, Vlodavsky L. Inhibition of heparanase activity and tumor metastasis by laminarin sulfate and synthetic phosphorothioate oligodeoxynucleotides. Int J Cancer. 1999; 83:424–431.

Gasic GJ. Role of plasma, platelets, and endothelial cells in tumor metastasis. Cancer Meta. 1984; 3:99–114.

Nieswandt B, Hafner M, Echtenacher B, Mannel DN. Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Res.1999; 59:1295–1300.

Borsig L, Wong R, Feramisco J, Nadeau DR, Varki NM, Varki A. Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis. Proc Natl Acad Sci USA. 2001; 98:3352–3357.

Subramaniam M, Saffaripour S, Van De WL, Frenette PS, Mayadas TN, Hynes RO. Role of endothelial selectins in wound repair. Am J Pathol. 1997; 150:1701–1709.

Talbott GA, Sharar SR, Harlan JM, Winn RK. Leukocyte-endothelial interactions and organ injury: the role of adhesion molecules. New Horiz. 1994; 2:545–554.

Cummings RD, Smith DF. The selectin family of carbohydrate- binding proteins: structure and importance of carbohydrate ligands for cell adhesion. Bioessays. 1992; 14:849–856.

Lee AE, Rogers LA, Longcroft JM, Jeffery RE. Reduction of metastasis in a murine mammary tumour model by heparin and polyinosinic-polycytidylic acid. Clin Exp Metastasis. 1990; 8:165–171.

Biancone L, Araki M, Araki K, Vassalli P, Stamenkovic I. Redirection of tumor metastasis by expression of E-selectin in vivo. J Exp Med. 1996; 183:581–587.

Borsig L, Wong R, Hynes RO, Varki NM, Varki A. Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis. Proc Natl Acad Sci USA. 2002; 99:2193–2198.

Koenig A, Norgard-Sumnicht K, Linhardt R, Varki A. Differential interactions of heparin and heparan sulfate glycosaminoglycans with the selectins. Implications for the use of unfractionated and low-molecular-weight heparins as therapeutic agents. J Clin Invest. 1998; 101:877–889.

Borsig L, Wong R, Feramisco J, Nadeau DR, Varki NM, Varki A. Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis. Proc Natl Acad Sci USA. 2001; 98:3352–3357.

Borsig L, Wong R, Hynes RO, Varki NM, Varki A. Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis. Proc Natl Acad Sci USA. 2002; 99:2193–2198.

Ludwig RJ, Boehme B, Podda M, Henschler R, Jager E, Tandi C. Endothelial P-selectin as a target of heparin action in experimental melanoma lung metastasis. Cancer Res. 2004;64:2743–5270.

Stevenson JL, Varki A, Borsig L. Heparin attenuates metastasis mainly due to inhibition of P- and L-selectin, but non-anticoagulant heparins can have additional effects. Thromb Res. 2007; 120 (2):107–111.

Colin S, Jeanny JC, Mascarelli F, Al-Mahmood S, Courtois Y, Labarre J. In vivo involvement of heparan sulfate proteoglycan in the bioavailability, internalization, and catabolism of exogenous basic fibroblast growth factor. Mol Pharmacol. 1999; 55:74–82.

Collen A, Smorenburg SM, Peters E, Lupu F, Koolwijk P, Noorden VC. Unfractionated and low-molecular-weight heparin affect fibrin structure and angiogenesis in vitro. Cancer Res. 2000; 60:6196–6200.

D’Amore PA. Capillary growth: a two-cell system. Semin Cancer Biol. 1992; 3:49–56.

Folkman J, Weisz PB, Joullie MM, Li WW, Ewing WR. Control of angiogenesis with synthetic heparin substitutes. Science. 1989; 243:1490–1493.

Soker S, Goldstaub D, Svahn CM, Vlodawsky l, Levi BZ, Neufeld G. Variations in the size and sulfation of heparin modulate the effect of heparin on the binding of VEGF165 to its receptors. Biochem Biophys Res Commun. 1994; 203:1339–1347.

Gohji K, Hirano H, Okamoto M, Kitazawa S, Toyoshima M, Katauoko Y. Expression of three extracellular matrix degradative enzymes in bladder cancer. Int J Cancer. 2001; 95:295–301.

Lepri A, Benelli U, Bernardini N, Bianchi F, Lupetti M, Danesi R. Effect of low molecular weight heparan sulphate on angiogenesis in the rat cornea after chemical cauterization. J Ocul Pharmacol. 1994; 10:273–280.

Jayson GC, Gallagher JT. Heparin oligosaccharides: inhibitors of the biological activity of bFGF on Caco-2 cells. Br J Cancer. 1997; 75:9–16.

Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol. 2006; 24:2903-2909.

Nieves DJ, Azmi NS, Xu R, Levy R, Yates E, Fernig DG. Monovalent maleimide functionalization of gold nano particles via copper-free click chemistry. Chem Comm. 2014; 50: 13157-13160.

Dosio F, Brusa P, Crosasso P, Arpicco S, Cattel L. Preparation, characterization and properties in vitro and in vivo of a paclitaxel albumin conjugate. J Control Rel. 1997;47:293-304.

Singla AK, Garg A, Aggarwal D. Paclitaxel and its formulations. Int J Pharm. 2002; 235:179-192.

Hou L, Yao J, Zhou J, Zhiang Q. Biomaterials Pharmacokinetics of a paclitaxel-loaded low-molecular-weight heparin-all-trans- retinoid acid conjugate ternary nanoparticulate drug delivery system. Biomaterials. 2012; 33(21): 5431–5440.

Chen JX, Liang Y, Liu W, Huang J, Chen H J. Fabrication of doxorubicin and heparin co-loaded microcapsules for synergistic cancer therapy. Int J Biol Macromol. 2014; 69: 554–560.

Zhao W, Lam JCF, Chiuman W, Brook MA, Li Y. Enzymatic cleavage of nucleic acids on gold nanoparticles: a generic platform for facile colorimetric biosensors. Small. 2008; 4:810-816.

Lin CJ, Yang T, Lee C, Huang SH, Sperling RA, Zanella M. Synthesis, characterization, and bioconjugation of fluorescent gold nanoclusters toward biological labeling applications. ACS Nano. 2009; 3:395-401.

Lee K, Lee H, Bae KH, Park TG. Heparin immobilized gold nanoparticles for targeted detection and apoptotic death of metastatic cancer cells. Biomaterials. 2010; 31(25):6530–6536.

Lee DY, Kim SK, Kim YS, Son DH, Nam JH, Kim IS. Suppression of angiogenesis and tumor growth by orally active deoxycholic acid-heparin conjugate. J Control Rel.2007; 118(3):310–317.

Shim G, Kim JY, Han J, Chuang SW, Lee S, Byun Y. Reduced graphene oxide nanosheets coated with an anti-angiogenic anticancer low-molecular-weight heparin derivative for delivery of anticancer drugs. J Control Rel. 2014; 189:80–89.

Downloads

Published

31.12.2014

How to Cite

Lokwani, R., Azmi, N. S., Mohd Yusoff, M., & Ichwan, S. J. A. (2014). Beyond anticoagulant: Heparin as a potential anti-cancer agent. Journal of Biochemistry, Microbiology and Biotechnology, 2(2), 76–82. https://doi.org/10.54987/jobimb.v2i2.160

Issue

Vol. 2 No. 2 (2014)

Section

Articles

License

Authors who publish with this journal agree to the following terms:

    1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
    2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
    3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).