Loading

International Journal of Plant Biology & Research

Plant Lectins in Therapeutic and Diagnostic Cancer Research

Review Article | Open Access

  • 1. School of Nutritional and Environmental Sciences, University of Shizuoka, Japan
  • 2. Faculty of Health Promotional Sciences, Tokoha University, Japan
+ Show More - Show Less
Corresponding Authors
Mamoru Isemura, School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka-422-8526, Japan, Tel & Fax: 81-54-264-5822
Abstract

Lectins are proteins or glycoprotein’s of non-immune origin that exhibit specific binding affinity for the carbohydrate moiety of glycol-conjugates. Several plant lectins have been shown to induce cell death in cancer cells, suggesting that these molecules may have applications in cancer treatments. Cancer cells are known to express and/ or secrete glycol-conjugates with an aberrant glycan structure. Thus, lectins may detect such changes, leading to their use in cancer diagnosis and cancer-specific treatment. Mistletoe lectins are representative of an anticancer drug target, and lentil lectin has been shown to have diagnostic applications in hepatocellular carcinoma. In this review, we describe recent progress in lectin researches, with special emphasis on the applications of plant lectins in human cancer diagnosis and therapy.

Citation

Pervin M, Koyama Y, Isemura M, Nakamura Y (2015) Plant Lectins in Therapeutic and Diagnostic Cancer Research. Int J Plant Biol Res 3(2): 1030.

Keywords

•    Plant lectin
•    Cancer therapy
•    Cancer diagnosis
•    Glycoproteins

ABBREVIATIONS

AFP: α-fetoprotein; ConA: Concanavalin A; HCC: Hepatocellular Carcinoma; LCA: Lens culinaris agglutinin; PNA: Arachis hypogea agglutinin; rVAA: ricommbinant Viscum album agglutinin; VAA: Viscum album agglutinin; VAE: Viscum album L. extracts; WFA: Wisteria floribunda agglutinin

INTRODUCTION

Lectins are proteins or glycoproteins of non-immune origin with specific binding affinity for the carbohydrate moiety of glycoconjugates [1,2]. Plant lectins exhibit a variety of biological activities, including cell agglutination, mitosis, toxicity, and cell growth inhibition. Several plant lectins have been shown to induce cell death in cancer cells, suggesting that they may have applications in cancer treatments. Cancer cells have been shown to express and/or secrete glycoconjugates with an aberrant glycan structure [3]. Thus, lectins may detect such changes, leading to their use in cancer diagnosis and cancer-specific treatment. Animal lectins have also been identified but plant lectins have attracted specific attention because of their ease of preparation and commercial availability which would make animal experiments feasible. The characteristics of plant lectins have been the subject of several comprehensive review articles [4-10].

In this review, we provide an update of recent progress in lectin researches, with special emphasis on the application of plant lectins in the treatment and diagnosis of human cancer.

The anticancer effects of plant lectins

Plant lectins have attracted attention because of their anticancer properties and potential application as antitumor agents; lectins are expected to be able to bind specifically to cancer cell membranes or receptors, causing cytotoxicity, apoptosis, autophagy [10,11], and inhibition of tumor growth.

Anticancer effects of mistletoe (Viscum album L.) extracts (VAE) and V. album agglutinins (VAA)

VAE and VAA have been widely studied as potential anticancer therapeutics or adjuvant therapeutic agents [12-14]. For example, patients with sarcoma achieved remission of tumor symptoms when they were subcutaneously administered VAE at an optimal dose of 0.75–1.0 ng/kg body weight twice a week [7].

A recent case report showed complete regression of colon adenoma after intratumoral injection with VAE in a 78-yearold man who had undergone hemicolectomy for stage IIIC colon cancer [13]. In another case, an 88-year-old man showed improvement in symptoms of adenoid cystic carcinoma following treatment with VAE, accompanied by a good quality of life and partial tumor regression [14]. Thus, while more clinical studies are required and the mechanisms are known only partly, VAE could be a promising anticancer agent.

Several studies have shown that VAA is one of the active components of VAE in terms of anticancer effects [15,16]. A clinical study in patients with stratified stage III/IV glioma showed a tendency for prolongation of relapse-free survival in patients treated with VAA (17.43 ± 8.2 months) versus the control group (10.45 ± 3.9 months) and a statistically significant extension of overall survival for patients treated with VAA (20.05 ± 3.5 months) as compared to the untreated group (9.90 ± 2.1 months) [16].

Schumacher et al. reported that recombinant VAA (rVAA) were successful in treating human ovarian cancer cells transplanted into severe combined immune deficient mice [17]. In an experiment using C57BL6 mice inoculated with B16- BL6 melanoma cells, Korean VAA inhibited tumor growth and metastasis by increasing apoptosis or type I programmed cell death and inhibiting angiogenesis [18].

A number of cellular experiments have indicated that VAA inhibit cell growth [5,6]. Janssen et al. demonstrated that purified VAE and VAA inhibited the growth of a variety of tumor cell lines, including B cell hybridomas and P815, EL-4, Ke37, MOLT-4, and U937 cells. The mechanism of growth arrest was shown to involve the induction of apoptosis [19]. European mistletoe lectin, VAA-I, was shown to accelerate apoptosis by shutting down the synthesis of proteins, including the anti-apoptotic protein Mcl-1 [20].

Japanese VAA also induced apoptosis in cancer cells. The lectin lead U937 cells to chromatin condensation and nucleosomal fragmentation which was blocked by a caspase inhibitor drug [21], similar to the findings with European VAA [22] (Figure 1). Therefore, one of the major causes of the anticancer effects of VAA is thought to be their ability to induce apoptosis. A mechanism involving autophagy has also been proposed [6,11] (Figure 1).

Another possible mechanism through which VAA exhibits anticancer activity may be associated with their immunomodulatory activities [12]. Hajto et al. demonstrated that 10 ng/mL VAA-I or 50 ng/mL rVAA induced a significant increase in the secretion of interleukin-12 in cultured human peripheral blood mononuclear cells. A single intravenous injection of 0.5–1 ng/kg of VAA-I into Wistar rats doubled the natural killer cell cytotoxicity of splenocytes against YAC-1 targets as compared to control animals. These results suggested that VAA augmented the secretion of the active form of interleukin-12 and potentiated cytokine-induced NK activation [23]. ML-J strongly enhanced the gene expression of certain pro-inflammatory cytokines in Caco-2 human colon carcinoma cells and in the mouse duodenum [2].

Future studies should examine the specific mechanisms through which VAE and VAA modulate the immune system in vivo in animal and human experiments.

RICIN

Ricin is a lectin found in the castor bean Ricinus communus, and ricin A-chain has RNA N-glycosidase activity, which inactivates eukaryotic ribosomes, thereby causing cytotoxicity [24]. Conjugates of ricin A-chain with antibodies against cancer cells have been developed as a therapeutic agent [25]. The results of a phase III study in 157 randomized patients with B-cell lymphoma showed that anti-B4-blocked ricin therapy tended to improve survival, although no significant differences were found in event-free survival and overall survival as compared with control observations [26].

Hara and Seon found that treatment with immunotoxins containing ricin A-chain completely or partially suppressed solid tumor growth in nude mice inoculated with MOLT-4 human T-cell leukemia cells [27]. Future studies are required to determine the applicability of ricin and its derivatives as anticancer drugs.

CONCANAVALIN A (CONA) AND OTHER LECTINS

ConA induces apoptotic morphology in cultured MCF-7 human breast carcinoma cells. When nude mice bearing MCF-7 cell-derived tumors were injected intraperitoneally with ConA (40 mg/kg) daily for 14 days, tumor volumes and weights decreased [28]. ConA induced apoptosis and autophagic death in HeLa cells through suppression of the phosphoinositol 3-kinase/ Akt/mammalian target of rapamycin pathway and promoted both autophagic and apoptotic cell death through reactive oxygen species generation in HeLa cells [29]. The potential of ConA as an anticancer agent with apoptotic, autophagic, and anti-angiogenic effects in cancer therapy has been described in a comprehensive review [30].

Similarly, several animal studies have suggested the potential usefulness of various lectins as therapeutic agents. A study on intraperitoneally administered Pisum sativum lectin at 2.8 mg/kg body weight showed reduced growth of Ehrlich ascites carcinoma, accompanied by increased red blood cell numbers and normal white blood cell numbers in mice, suggesting the usefulness of this lectin for cancer therapy. The mechanism of inhibition of tumor growth in mice was shown to involve apoptosis by cell cycle arrest at G2 /M phase via increased expression of proapoptotic Bax and reduced expression of anti-apoptotic Bcl-2 and Bcl-XL [31]. In another study, administration of 100 mg/kg body weight Lycoris aurea agglutinin reduced the volume and weight of subcutaneous tumors derived from A549 cells in nude mice via an apoptotic pathway [32].

Recent animal studies have demonstrated the anti-tumor effects of several lectins as exemplified below. Abrus precatorius agglutinin, a ribosome inactivating lectin inhibited the tumor growth in nude mice bearing xenografts of human hepatoma HepG2 cells [33]. In vivo administration of Arachis hypogea agglutinin (PNA) reduced tumor cell proliferation in mice bearing Dalton’s lymphoma with increase in autophagic and apoptotic characteristics [34]. Similarly Glycin max lectin inhibited tumor cell proliferation in mice bearing Dalton’s lymphoma [35]. D-galactose-specific Momordica charantia lectin showed dosedependent inhibition of growth of Ehrlich ascites carcinoma cells in mice when administered intraperitoneally [36]. Experimental therapy in vivo showed that Pinella ternate lectin inhibited proliferation of transplanted Sarcoma 180 cells in mice [37]. Flow cytometric analysis demonstrated that the inhibition mechanism involved induction of G0/G1 cell cycle arrest.

In addition, a number of experiments have used cultured human cell lines to determine a mechanism through which lectins exhibit anticancer activity. For example, soybean lectin was found to induce both apoptotic and autophagic cell death in HeLa cells by a pathway mediated by reactive oxygen speciesdependent caspase activation [35]. Several other recent cellular experiments are listed in (Table 1) [38-50].

Table 1: Effect of lectins on cell death of human cancer cells.

Source of lectin Cancer cell type Cell growth inhibition/apoptosis/autophagic cell death Reference
Abelmoschus esculentusL. Breastcarcinoma MCF7 Apoptosis [38]
Astragalus membranaceusL. Leukemia CML K562 Apoptosis [39]
Bauhinia ungulata L. Colon adenocarcinoma HT-29 Cell growth inhibition [40]
Bauhinia forficata Breastcarcinoma MCF7 Cell growth inhibition [41]
Canavalia ensiformis, Canavalia brasiliensis Leukemia MOLT4, HL-60 Apoptosis [42]
Dioscorea opposite Breast cancer MCF7, hepatoma HepG2, nasopharyngeal carcinoma CNE2 Apoptosis [43]
Lotus corniculatus Leukemia THP1, lung cancer HOP62, colon cancer HCT116 Cell growth inhibition, apoptosis [44]
Morus alba L. Breast cancer MCF7, colon cancer HCT15 Apoptosis [45]
Phaseolus vulgaris cv. Breast cancer MCF7, hepatoma HepG2, nasopharyngeal carcinoma CNE1 and CNE2 Cell growth inhibition [46]
Phaseolus vulgaris cv. Breast cancer MCF7 Cell growth inhibition [47]
Phaseolus vulgariscv. Breast cancer MCF7, nasopharyngeal carcinoma, HONE1 Cell growth inhibition [48]
Polygonatum odoratum breast cancer MCF7 Apoptosis, autophagic  cell death [49]
Sophora alopecuroides Cervical cancer HeLa, esophageal cancer Eca109 Cell growth inhibition [50]

 

CONCLUDING REMARKS

As addressed in this review, lectins appear to be promising targets for therapeutic and diagnostic cancer research. Administration of lectins has not been shown to cause deleterious effects in general. For example, when VAE were injected subcutaneously in healthy male volunteers, VAA was detected in serum, and no serious adverse effects were detected [71]. Although high doses of rVAA has been shown to result in reversible hepatotoxicity in some cases, administration of rVAA in humans was not accompanied by immune-suppression and had a low risk of adverse effects overall [12].

On the other hand, ConA has been shown to induce hepatitis in murine models [72]. Dietary LCA was shown to upregulate cancer-associated gene expression in the mouse duodenum, suggesting that the lectin may promote colorectal cancer [73]. Therefore, clinical application of lectins should be monitored carefully by clinicians, and more studies on the adverse effects of lectins, including carcinogenesis induced by plant lectins, are needed.

ACKNOWLEDGEMENTS

We thank Dr. Yutaka Aoyagi, Professor Emeritus at Niigata University for providing us with permission to use data of his study group.

REFERENCES

1. Goldstein ZJ, Hughes RC, Monsigny M, Osawa T, Sharon N. What should be called a lectin?. Nature. 1980; 285: 66.

2. Monira P, Koyama Y, Fukutomi R, Yasui K, Isemura M, Yokogoshi H. Effects of Japanese mistletoe lectin on cytokine gene expression in human colonic carcinoma cells and in the mouse intestine. Biomed Res. 2009; 30: 303-309.

3. Kjeldsen T, Clausen H, Hirohashi S, Ogawa T, Iijima H, Hakomori S. Preparation and characterization of monoclonal antibodies directed to the tumor-associated O-linked sialosyl-2----6 alpha-N-acetylgalactosaminyl (sialosyl-Tn) epitope. Cancer Res. 1988; 48: 2214-2220.

4. Aoyagi Y. Molecular discrimination between alpha-fetoprotein from patients with hepatocellular-carcinoma and nonneoplastic liver-diseases by their carbohydrate structures (review). Int J Oncol. 1994; 4: 369-383.

5. Zwierzina H, Bergmann L, Fiebig H, Aamdal S, Schöffski P, Witthohn K, et al. The preclinical and clinical activity of aviscumine: a potential anticancer drug. Eur J Cancer. 2011; 47: 1450-1457.

6. Fu LL, Zhou CC, Yao S, Yu JY, Liu B, Bao JK. Plant lectins: targeting programmed cell death pathways as antitumor agents. Int J Biochem Cell Biol. 2011; 43: 1442-1449.

7. Kirsch A, Hajto T. Case reports of sarcoma patients with optimized lectin-oriented mistletoe extract therapy. J Altern Complement Med. 2011; 17: 973-979.

8. Souza MA, Carvalho FC, Ruas LP, Ricci-Azevedo R, Roque-Barreira MC. The immunomodulatory effect of plant lectins: a review with emphasis on ArtinM properties. Glycoconj J. 2013; 30: 641-657.

9. Huang TS, Shyu YC, Turner R, Chen HY, Chen PJ. Diagnostic performance of alpha-fetoprotein, lens culinaris agglutinin-reactive alpha-fetoprotein, des-gamma carboxyprothrombin, and glypican-3 for the detection of hepatocellular carcinoma: a systematic review and meta-analysis protocol. Syst Rev. 2013; 2: 37.

10. Liu Z, Luo Y, Zhou TT, Zhang WZ. Could plant lectins become promising anti-tumour drugs for causing autophagic cell death? Cell Prolif. 2013; 46: 509-515.

11. Liu B, Bian HJ, Bao JK. Plant lectins: potential antineoplastic drugs from bench to clinic. Cancer Lett. 2010; 287: 1-12.

12. Kienle GS, Grugel R, Kiene H. Safety of higher dosages of Viscum album L. in animals and humans--systematic review of immune changes and safety parameters. BMC Complement Altern Med. 2011; 11: 72.

13. von Schoen-Angerer T, Goyert A, Vagedes J, Kiene H, Merckens H, Kienle GS. Disappearance of an advanced adenomatous colon polyp after intratumoural injection with Viscum album (European mistletoe) extract: a case report. J Gastrointestin Liver Dis. 2014; 23: 449-452.

14. Werthmann PG, Helling D, Heusser P, Kienle GS. Tumour response following high-dose intratumoural application of Viscum album on a patient with adenoid cystic carcinoma. BMJ Case Rep. 2014; 2014.

15. Büssing A, Schietzel M. Apoptosis-inducing properties of Viscum album L. extracts from different host trees, correlate with their content of toxic mistletoe lectins. Anticancer Res. 1999; 19: 23-28.

16. Lenartz D, Dott U, Menzel J, Schierholz JM, Beuth J. Survival of glioma patients after complementary treatment with galactoside-specific lectin from mistletoe. Anticancer Res. 2000; 20: 2073-2076.

17. Schumacher U, Feldhaus S, Mengs U. Recombinant mistletoe lectin (rML) is successful in treating human ovarian cancer cells transplanted into severe combined immunodeficient (SCID) mice. Cancer Lett. 2000; 150: 171-175.

18. Park WB, Lyu SY, Kim JH, Choi SH, Chung HK, Ahn SH, et al. Inhibition of tumor growth and metastasis by Korean mistletoe lectin is associated with apoptosis and antiangiogenesis. Cancer Biother Radiopharm. 2001; 16: 439-447.

19. Janssen O, Scheffler A, Kabelitz D. In vitro effects of mistletoe extracts and mistletoe lectins. Cytotoxicity towards tumor cells due to the induction of programmed cell death (apoptosis). Arzneimittelforschung.1993; 43: 1221-1227.

20. Lavastre V, Pelletier M, Saller R, Hostanska K, Girard D. Mechanisms involved in spontaneous and Viscum album agglutinin-I-induced human neutrophil apoptosis: Viscum album agglutinin-I accelerates the loss of antiapoptotic Mcl-1 expression and the degradation of cytoskeletal paxillin and vimentin proteins via caspases. J Immunol. 2002; 168: 1419-1427.

21. Koyama Y, Suzuki T, Kajiya A, Matsushita Y, Odani S, Kawakami et.al. Simple purification method of lectins-application to isolation of a Japanese mistletoe lectin. Curr Topics Biotechnol. 2004; 1: 67-73.

22. Miyoshi N, Koyama Y, Katsuno Y, Hayakawa S, Mita T, Ohta T, et al. Apoptosis induction associated with cell cycle dysregulation by rice bran agglutinin. J Biochem. 2001; 130: 799-805.

23. Hajto T, Hostanska K, Weber K, Zinke H, Fischer J, Mengs U, et al. Effect of a recombinant lectin, Viscum album agglutinin on the secretion of interleukin-12 in cultured human peripheral blood mononuclear cells and on NK-cell-mediated cytotoxicity of rat splenocytes in vitro and in vivo. Nat Immun. 1998; 16: 34-46.

24. Endo Y, Tsurugi K. RNA N-glycosidase activity of ricin A-chain. Mechanism of action of the toxic lectin ricin on eukaryotic ribosomes. J Biol Chem. 1987; 262: 8128-8130.

25. Weidle UH, Tiefenthaler G, Schiller C, Weiss EH, Georges G, Brinkmann U. Prospects of bacterial and plant protein-based immunotoxins for treatment of cancer. Cancer Genomics Proteomics. 2014; 11: 25-38.

26. Furman RR, Grossbard ML, Johnson JL, Pecora AL, Cassileth PA, Jung SH, et.al. Cancer Leukemia Group B; Eastern Cooperative Oncology Group. A phase III study of anti-B4-blocked ricin as adjuvant therapy post-autologous bone marrow transplant: CALGB 9254. Leuk Lymphoma.2011; 52: 587-596.

27. Hara H, Seon BK. Complete suppression of in vivo growth of human leukemia cells by specific immunotoxins: nude mouse models. Proc Natl Acad Sci U S A. 1987; 84: 3390-3394.

28. Shi Z, Chen J, Li CY, An N, Wang ZJ, Yang SL, et al. Antitumor effects of concanavalin A and Sophora flavescens lectin in vitro and in vivo. Acta Pharmacol Sin. 2014; 35: 248-256.

29. Roy B, Pattanaik AK, Das J, Bhutia SK, Behera B, Singh P, et al. Role of PI3K/Akt/mTOR and MEK/ERK pathway in Concanavalin A induced autophagy in HeLa cells. Chem Biol Interact. 2014; 210: 96-102.

30. Li WW, Yu JY, Xu HL, Bao JK. Concanavalin A: a potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis for cancer therapeutics. Biochem Biophys Res Commun. 2011; 414: 282-286.

31. Kabir SR, Nabi MM, Haque A, Rokon Uz Zaman, Mahmud ZH, Reza MA. Pea lectin inhibits growth of Ehrlich ascites carcinoma cells by inducing apoptosis and G2/M cell cycle arrest in vivo in mice. Phytomedicine. 2013; 20: 1288-1296.

32. Li CY, Wang Y, Wang HL, Shi Z, An N, Liu YX, et al. Molecular mechanisms of Lycoris aurea agglutinin-induced apoptosis and G2 /M cell cycle arrest in human lung adenocarcinoma A549 cells, both in vitro and in vivo. Cell Prolif. 2013; 46: 272-282.

33. Mukhopadhyay S, Panda PK, Das DN, Sinha N, Behera B, Maiti TK, et al. Abrus agglutinin suppresses human hepatocellular carcinoma in vitro and in vivo by inducing caspase-mediated cell death. Acta Pharmacol Sin. 2014; 35: 814-824.

34. Mukhopadhyay S, Panda PK, Behera B, Das CK, Hassan MK, Das DN, et al. In vitro and in vivo antitumor effects of Peanut agglutinin through induction of apoptotic and autophagic cell death. Food Chem Toxicol. 2014; 64: 369-377.

35. Panda PK, Mukhopadhyay S, Behera B, Bhol CS, Dey S, Das DN, et al. Antitumor effect of soybean lectin mediated through reactive oxygen species-dependent pathway. Life Sci. 2014; 111: 27-35.

36. Kabir SR, Nabi MM, Nurujjaman M, Reza MA, Alam AH, Zaman RU, et al. Momordica charantia Seed Lectin: Toxicity, Bacterial Agglutination and Antitumor Properties. Appl Biochem Biotechnol. 2015; 175: 2616-2628.

37. Zuo Z, Fan H, Wang X, Zhou W, Li L. Purification and characterization of a novel plant lectin from Pinellia ternata with antineoplastic activity. Springerplus. 2012; 1: 13.

38. Monte LG, Santi-Gadelha T, Reis LB, Braganhol E, Prietsch RF, Dellagostin OA, et al. Lectin of Abelmoschus esculentus (okra) promotes selective antitumor effects in human breast cancer cells. Biotechnol Lett. 2014; 36: 461-469.

39. Huang LH, Yan QJ, Kopparapu NK, Jiang ZQ, Sun Y. Astragalus membranaceus lectin (AML) induces caspase-dependent apoptosis in human leukemia cells. Cell Prolif. 2012; 45: 15-21.

40. Silva HC, Pinto LS, Teixeira EH, Nascimento KS, Cavada BS, Silva ALC. A novel lectin from Bauhinia ungulata L. seeds with fungistaticand antiproliferative activities. Process Biochem. 2014; 49: 203-209.

41. Silva MC, de Paula CA, Ferreira JG, Paredes-Gamero EJ, Vaz AM, Sampaio MU, et al. Bauhinia forficata lectin (BfL) induces cell death and inhibits integrin-mediated adhesion on MCF7 human breast cancer cells. Biochim Biophys Acta. 2014; 1840: 2262-2271.

42. Faheina-Martins GV, da Silveira AL, Cavalcanti BC, Ramos MV, Moraes MO, Pessoa C, et al. Antiproliferative effects of lectins from Canavalia ensiformis and Canavalia brasiliensis in human leukemia cell lines. Toxicol In Vitro. 2012; 26: 1161-1169.

43. Chan YS, Ng TB. A lectin with highly potent inhibitory activity toward breast cancer cells from edible tubers of Dioscorea opposita cv. nagaimo. PLoS One. 2013; 8: e54212.

44. Rafiq S, Majeed R, Qazi AK, Ganai BA, Wani I, Rakhshanda S, et al. Isolation and antiproliferative activity of Lotus corniculatus lectin towards human tumour cell lines. Phytomedicine. 2013; 21: 30-38.

45. Deepa M, Sureshkumar T, Satheeshkumar PK, Priya S. Purified mulberry leaf lectin (MLL) induces apoptosis and cell cycle arrest in human breast cancer and colon cancer cells. Chem Biol Interact. 2012; 200: 38-44.

46. Chan YS, Wong JH, Fang EF, Pan W, Ng TB. Isolation of a glucosamine binding leguminous lectin with mitogenic activity towards splenocytes and anti-proliferative activity towards tumor cells. PLoS One. 2012; 7: e38961.

47. Cheung RC, Leung HH, Pan WL, Ng TB. A calcium ion-dependent dimeric bean lectin with antiproliferative activity toward human breast cancer MCF-7 cells. Protein J. 2013; 32: 208-215.

48. Ang ASW, Cheung RCF, Dan X, Chan YS, Pan W, Ng TB. Purification and characterization of a glucosamine-binding antifungal lectin from Phaseolus vulgaris cv. Chinese pinto beans with antiproliferative activity towards nasopharyngeal carcinoma cells. Appl Biochem Biotechnol. 2014; 172:672-686.

49. Ouyang L, Chen Y, Wang XY, Lu RF, Zhang SY, Tian M, Xie T. Polygonatum odoratum lectin induces apoptosis and autophagy via targeting EGFR-mediated Ras-Raf-MEK-ERK pathway in human MCF-7 breast cancer cells. Phytomedicine. 2014; 21: 1658-1665.

50. Li T, Yin X, Liu D, Ma X, Lv H, Sun S. Isolation and characterization of a novel lectin with antifungal and antiproliferative activities from Sophora alopecuroides seeds. Acta Biochim Biophys Sin (Shanghai). 2012; 44: 606-613.

51. Yi X, Yu S, Bao Y. Alpha-fetoprotein-L3 in hepatocellular carcinoma: a meta-analysis. Clin Chim Acta. 2013; 425: 212-220.

52. Aoyagi Y, Suzuki Y, Isemura M, Soga K, Ozaki T, Ichida T, et al. Differential reactivity of alpha-fetoprotein with lectins and evaluation of its usefulness in the diagnosis of hepatocellular carcinoma. Gan. 1984; 75: 809-815.

53. Taketa K, Hirai H. Lectin affinity electrophoresis of alpha-fetoprotein in cancer diagnosis. Electrophoresis. 1989; 10: 562-567.

54. Aoyagi Y. Alpha-fetoprotein as a tumor marker for hepatocellular carcinoma — from quantitative to qualitative evaluation. Frontiers Gastroenterol. 2005; 10: 14-29.

55. Shimizu K, Taniichi T, Satomura S, Matsuura S, Taga H, Taketa K. Establishment of assay kits for the determination of microheterogeneities of alpha-fetoprotein using lectin-affinity electrophoresis. Clin Chim Acta. 1993; 214: 3-12.

56. Qi YJ, Ward DG, Pang C, Wang QM, Wei W, Ma J, et al. Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma. Proteomics. 2014; 14: 186-195.

57. Yang G, Cui T, Wang Y, Sun S, Ma T, Wang T, et al. Selective isolation and analysis of glycoprotein fractions and their glycomes from hepatocellular carcinoma sera. Proteomics. 2013; 13: 1481-1498.

58. Matsuda A, Kuno A, Matsuzaki H, Kawamoto T, Shikanai T, Nakanuma Y, et.al. Glycoproteomics-based cancer marker discovery adopting dual enrichment with Wisteria floribunda agglutinin for high specific glyco-diagnosis of cholangiocarcinoma. J Proteomics. 2013; 85: 1-11.

59. Sogabe M, Nozaki H, Tanaka N, Kubota T, Kaji H, Kuno A, et al. Novel glycobiomarker for ovarian cancer that detects clear cell carcinoma. J Proteome Res. 2014; 13: 1624-1635.

60. Silva ML, Gutiérrez E, Rodríguez JA, Gomes C, David L. Construction and validation of a Sambucus nigra biosensor for cancer-associated STn antigen. Biosens Bioelectron. 2014; 57: 254-261.

61. Drake P, Schilling B, Gibson B, Fisher S. Elucidation of N-glycosites within human plasma glycoproteins for cancer biomarker discovery. Methods Mol Biol. 2013; 951: 307-322.

62. Li N, Chow AM, Ganesh HV, Brown IR, Kerman K. Quantum dot based fluorometric detection of cancer TF-antigen. Anal Chem. 2013; 85: 9699-9704.

63. Sakuma S, Yamashita S, Hiwatari K, Hoffman RM, Pham W. Lectinimmobilized fluorescent nanospheres for targeting to colorectal cancer from a physicochemical perspective. Curr Drug Discov Technol. 2011; 8: 367-378.

64. Sakuma S, Higashino H, Oshitani H, Masaoka Y, Kataoka M, Yamashita S, et.al. Essence of affinity and specificity of peanut agglutinin-immobilized fluorescent nanospheres with surface poly(N-vinylacetamide) chains for colorectal cancer. Eur J Pharm Biopharm. 2011; 79: 537-543.

65. Oliveira C, Teixeira JA, Domingues L. Recombinant production of plant lectins in microbial systems for biomedical application - the frutalin case study. Front Plant Sci. 2014; 5: 390.

66. Nakajima K, Inomata M, Iha H, Hiratsuka T, Etoh T, Shiraishi N, et al. Establishment of new predictive markers for distant recurrence of colorectal cancer using lectin microarray analysis. Cancer Med. 2015; 4: 293-302.

67. Fukasawa T, Asao T, Yamauchi H, Ide M, Tabe Y, Fujii T, et al. Associated expression of α 2,3sialylated type 2 chain structures with lymph node metastasis in distal colorectal cancer. Surg Today. 2013; 43: 155-162.

68. Marangoni VS, Paino IM, Zucolotto V. Synthesis and characterization of jacalin-gold nanoparticles conjugates as specific markers for cancer cells. Colloids Surf B Biointerfaces. 2013; 112: 380-386.

69. Soga K, Teruya F, Tateno H, Hirabayashi J, Yamamoto K. Terminal N-acetylgalactosamine-specific leguminous lectin from Wisteria japonica as a probe for human lung squamous cell carcinoma. PLoS One. 2013; 8: e83886.

70. Mitsui Y, Yamada K, Hara S, Kinoshita M, Hayakawa T, Kakehi K. Comparative studies on glycoproteins expressing polylactosaminetype N-glycans in cancer cells. J Pharm Biomed Anal. 2012; 70: 718- 726.

71. Huber R, Eisenbraun J, Miletzki B, Adler M, Scheer R, Klein R, Gleiter CH. Pharmacokinetics of natural mistletoe lectins after subcutaneous injection. Eur J Clin Pharmacol. 2010; 66: 889-897.

72. Tsutsui H, Nishiguchi S. Importance of Kupffer cells in the development of acute liver injuries in mice. Int J Mol Sci. 2014; 15: 7711-7730.

73. Pervin M, Paeng N, Yasui K, Imai S, Isemura M, Yokogoshi H, Nakayama T. Effects of Lens culinaris agglutinin on gene expression of gluconeogenic enzymes in the mouse intestine. J Sci Food Agric. 2012; 92: 857-861.

Received : 09 Feb 2015
Accepted : 01 Apr 2015
Published : 04 Apr 2015
Journals
Annals of Otolaryngology and Rhinology
ISSN : 2379-948X
Launched : 2014
JSM Schizophrenia
Launched : 2016
Journal of Nausea
Launched : 2020
JSM Internal Medicine
Launched : 2016
JSM Hepatitis
Launched : 2016
JSM Oro Facial Surgeries
ISSN : 2578-3211
Launched : 2016
Journal of Human Nutrition and Food Science
ISSN : 2333-6706
Launched : 2013
JSM Regenerative Medicine and Bioengineering
ISSN : 2379-0490
Launched : 2013
JSM Spine
ISSN : 2578-3181
Launched : 2016
Archives of Palliative Care
ISSN : 2573-1165
Launched : 2016
JSM Nutritional Disorders
ISSN : 2578-3203
Launched : 2017
Annals of Neurodegenerative Disorders
ISSN : 2476-2032
Launched : 2016
Journal of Fever
ISSN : 2641-7782
Launched : 2017
JSM Bone Marrow Research
ISSN : 2578-3351
Launched : 2016
JSM Mathematics and Statistics
ISSN : 2578-3173
Launched : 2014
Journal of Autoimmunity and Research
ISSN : 2573-1173
Launched : 2014
JSM Arthritis
ISSN : 2475-9155
Launched : 2016
JSM Head and Neck Cancer-Cases and Reviews
ISSN : 2573-1610
Launched : 2016
JSM General Surgery Cases and Images
ISSN : 2573-1564
Launched : 2016
JSM Anatomy and Physiology
ISSN : 2573-1262
Launched : 2016
JSM Dental Surgery
ISSN : 2573-1548
Launched : 2016
Annals of Emergency Surgery
ISSN : 2573-1017
Launched : 2016
Annals of Mens Health and Wellness
ISSN : 2641-7707
Launched : 2017
Journal of Preventive Medicine and Health Care
ISSN : 2576-0084
Launched : 2018
Journal of Chronic Diseases and Management
ISSN : 2573-1300
Launched : 2016
Annals of Vaccines and Immunization
ISSN : 2378-9379
Launched : 2014
JSM Heart Surgery Cases and Images
ISSN : 2578-3157
Launched : 2016
Annals of Reproductive Medicine and Treatment
ISSN : 2573-1092
Launched : 2016
JSM Brain Science
ISSN : 2573-1289
Launched : 2016
JSM Biomarkers
ISSN : 2578-3815
Launched : 2014
JSM Biology
ISSN : 2475-9392
Launched : 2016
Archives of Stem Cell and Research
ISSN : 2578-3580
Launched : 2014
Annals of Clinical and Medical Microbiology
ISSN : 2578-3629
Launched : 2014
JSM Pediatric Surgery
ISSN : 2578-3149
Launched : 2017
Journal of Memory Disorder and Rehabilitation
ISSN : 2578-319X
Launched : 2016
JSM Tropical Medicine and Research
ISSN : 2578-3165
Launched : 2016
JSM Head and Face Medicine
ISSN : 2578-3793
Launched : 2016
JSM Cardiothoracic Surgery
ISSN : 2573-1297
Launched : 2016
JSM Bone and Joint Diseases
ISSN : 2578-3351
Launched : 2017
JSM Bioavailability and Bioequivalence
ISSN : 2641-7812
Launched : 2017
JSM Atherosclerosis
ISSN : 2573-1270
Launched : 2016
Journal of Genitourinary Disorders
ISSN : 2641-7790
Launched : 2017
Journal of Fractures and Sprains
ISSN : 2578-3831
Launched : 2016
Journal of Autism and Epilepsy
ISSN : 2641-7774
Launched : 2016
Annals of Marine Biology and Research
ISSN : 2573-105X
Launched : 2014
JSM Health Education & Primary Health Care
ISSN : 2578-3777
Launched : 2016
JSM Communication Disorders
ISSN : 2578-3807
Launched : 2016
Annals of Musculoskeletal Disorders
ISSN : 2578-3599
Launched : 2016
Annals of Virology and Research
ISSN : 2573-1122
Launched : 2014
JSM Renal Medicine
ISSN : 2573-1637
Launched : 2016
Journal of Muscle Health
ISSN : 2578-3823
Launched : 2016
JSM Genetics and Genomics
ISSN : 2334-1823
Launched : 2013
JSM Anxiety and Depression
ISSN : 2475-9139
Launched : 2016
Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
Journal of Drug Design and Research
ISSN : 2379-089X
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
JSM Surgical Oncology and Research
ISSN : 2578-3688
Launched : 2016
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
Clinical Research in Infectious Diseases
ISSN : 2379-0636
Launched : 2013
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Journal of Immunology and Clinical Research
ISSN : 2333-6714
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
Author Information X