CYTOTOXIC ACTIVITY OF ACIDIC RIBOSOME INACTIVATING PROTEINS MIRABILIS JALAPA L. (RIP MJ-C) NANOPARTICLE FORMULATED WITH LOW-CHAIN CHITOSAN AND LOW-METHYLATED PECTIN
DOI:
https://doi.org/10.22159/ijpps.2017v9i8.18171Keywords:
RIP MJ-C, Mirabilis jalapa L, Nanoparticle, Low-chain chitosan, Low-methylated pectinAbstract
Objective: This study aimed to formulate acidic ribosome inactivating protein isolated from Mirabilis jalapa L. (RIP MJ-C) nanoparticle, using low chains chitosan and low methylated pectin, and to evaluate its cytotoxic activity against T47D breast cancer cell line.
Methods: RIP MJ-C was isolated from Mirabilis jalapa L leaves using ion exchange chromatography method, and its presence was tested using super coiled double-stranded deoxyribonucleic acid (DNA) cleavage activity. The nanoparticle of RIP MJ-C was formulated using low chains chitosan and low methylated pectin. The optimum formula was characterised using transmission electron microscope (TEM) and particle size analyzer. The cytotoxic activity of the nanoparticle against T47D breast cancer cell-lines was assessed using MTT assay.
Results: The optimum formula was obtained at the combination of 0.06% low chain chitosan and 0.02% low methylated pectin. It was revealed that the nanoparticles have a particle size of 54.43±10.14 nm, polydispersity index of 0.514±0.10, and zeta potential of+93.59±6.90 mV. The cytotoxic activity test showed that RIP MJ-C nanoparticles conjugated with anti-EpCAM 9C4 have the highest cell death percentage of 43.20% compared to unformulated RIP MJ-C.
Conclusion: It was concluded that the RIP MJ-C nanoparticle conjugated with an anti-EpCAM antibody could enhance the cytotoxicity of RIP MJ-C against T47D breast cancer cell-lines.Â
Downloads
References
Ikawati Z, Sudjadi, Sismindari. Cytotoxicity against tumor cell lines of ribosome-inactivating protein (RIP)-like protein isolated from Mirabilis jalapa L. Malays J Pharm Sci 2006;4:1-11.
Sudjadi, Sismindari, Herawati T. Purification of ribosome inactivating protein (RIP) from Mirabilis jalapa L. leave with CM-sepharose CL-6B and Seph acryl S-300HR column. Indonesian J Pharm 2003;2:316–21.
Sudjadi, Witasari LD, Sadarum MT, Nastity N, Sismindari. Cytotoxic effect of protein such as ribosome inactivating protein (RIP) acid from Mirabilis jalapa L. leaves against cancer cells. Indonesian J Pharm 2007;1:8–14.
Citores L, Iglesias R, Ferreras J. Ribosome inactivating proteins from plants: biological properties and their use in experimental therapy in antitumor potential and other emerging medical properties of natural compounds. New York: Springer; 2013. p. 127–43.
De Virgilio M, Lombardi A, Caliandro R. Ribosome-inactivating proteins: from plant defence to tumor attack. Toxins 2011;2:2699–737.
Lankalapalli S, Kollapal V. Polyelectrolyte complexes: a review of their applicability in drug delivery technology. Indian J Pharm Sci 2009;71:481–7.
Leon L, Carvalho ELS, Seijo B, Ortega-Vinuesa JL, Bastos-González D. Physicochemical characterization of chitosan nanoparticles: electro-kinetic and stability behavior. J Colloid Interface Sci 2005;283:344–51.
Rawat M, Singh D, Saraf S, Saraf S. Nanocarriers: a promising vehicle for bioactive drugs. Biol Pharm Bull 2006;29:1790–8.
Shaima C, Moorthi PV, Kutty SN. In vitro anticancer activity of 5’ fluo uracil coated chitosan nanoparticle. Int J Curr Pharm Res 2016;8:6-8.
Pertiwi D, Martien R, Sismindari, Ismail H. Nanoparticle formulation of targeted ribosome inactivating protein Mirabillis jalapa (RIP MJ) using pectin-chitosan short chains conjugated by antibody anti-EpCAM and cytotoxic test against breast cancer cells. Pak J Pharm Sci 2017. Article In Press.
Feranisa A, Arimurni DA, Ismail H, Martien R, Sismindari. Formulation of medium viscosity chitosan-pectin–mj protein nano particles conjugated with anti-EpCAM and its cytotoxicity against T47D breast cancer cell lines. Int J Biotech 2015;20:1-10.
Wicaksono PA, Sismindari, Martien R, Ismail H. Formulation and Ribosome inactivating protein Mirabilis jalapa L (RIP-MJ) nanoparticles cytotoxicity test using the low viscosity of alginate-cytosan conjugated by antibody anti-epcam againts T47D cells. Asian Pac J Cancer Prev 2016;17:2277-84.
Dhar S, Kolishetti N, Lippard SJ, Farokhzad OC. Targeted delivery of a cisplatin prodrug for safer and more effective prostate cancer therapy in vivo. Proc Natl Acad Sci U S A 2011;108:1850–5.
Min K, Jo H, Song K, Cho M, Chun, Jon S. Dual-aptamer-based delivery vehicle of doxorubicin to both PSMA (+) and PSMA (−) prostate cancers. Biomaterials 2011;32:2124–32.
Ozalp VC, Eyidogan F, Oktem HA. Aptamer-gated nanoparticles for smart drug delivery. Pharmaceuticals 2011;4:1137–57.
Osta W, Chen Y, Mikhitarian K, Mitas M, Salem M, Hannun Y. EpCAM is overexpressed in breast cancer and a potential target for breast cancer gene therapy. Cancer Res 2004;64:5818-24.
Sismindari, Lord JM. The rna-n-glycosidase activity of leaves crude extract from Carica papaya, Morinda citrifolia, Mirabilis yalapa. Int J Biotech 2000;Suppl:342-5.
Martien R, Adhyatmika, Irianto DI, Farida V, Purwita SD. Development of nanoparticles technology as drug release system. Indonesian J Pharm 2012;3:1-5.
Nobel A. Quick StartTM bradford protein assay instruction manual. Hercules (CA): Bio-Rad Laboratories; 2000.
Sismindari, Hartati MS, Adhyatmika. Cytotoxic selectivity of MJC0.3 and MJC0.5, acidic ribosome-inactivating proteins isolated from Mirabilis jalapa L. leaves against various cancer cell-lines. J Med Sci 2010;42:39–43.
Ling J, Liu W, Wang TP. Cleavage of supercoiled double-stranded DNA by several ribosome-inactivating proteins in vitro. FEBS Lett 2009;345:143–6.
Nidhin M, Indumathy R, Sreeram KJ, Nair BU. Synthesis of iron oxide nanoparticles of narrow size distribution on polysaccharide templates. Bull Mater Sci 2008;31:93–6.
Mohanraj V, Chen Y. Nanoparticles: a review. Trop J Pharm Res 2006;1:561–73.
Tiyaabonchai W. Chitosan nanoparticles: a promising system for drug delivery. Naresuan University J 2003;2:51–66.
Adhyatmika (Thesis). Preparation of pentagamavunon-0 nanoparticles using matrix polymer of moderate chains chitosan and natrium tripolyphosphate cross-hook through ionic gelation mechanism as an anti-inflammation drug candidate. Yogyakarta: Universitas Gadjah Mada; 2012.
Published
How to Cite
Issue
Section
