Jure Leaf Extract (Nerium indium Mill.) Increased 5-Fluorouracil Sensitivity through Inhibition of NF-κB Activation and Transporter Protein in WiDr Colon Cancer Cell
Abstract
5-Fluorouracil (5-FU) is the first line chemotherapeutic agents for colon cancer therapy. Long term used of 5-FU caused cancer cell resistency. Thus, co-chemoteraputics agent should be developed to increase cells sensitivty towards 5-FU. Jure leaf (Nerium indicum Mill) extract (JLE) contains oleandrin which has cytotoxic effect on colon cancer cell. The ain of this study was to investigated the mechanism of JLE to sensitized colon cancer cell toward 5-FU through NF-κB inhibition and MRP protein repression. JLE was extracted by soxhletation method. Based on molecular docking to MRP protein, docking score of oleandrin (-50,496) was higher than native ligand ATP (-125,817). Oleandrin could interfere interaction with MRP. JLE increased 5-FU sensitivity a dose of 2 µg/mL JLE dan 12,5 µM 5-FU with the combination index (CI) of 0,594. Combination of JLE and 5-FU also inhibit p65 protein expression on WiDr cell.
Keywords: cytotoxic, Nerium indicum Mill., oleandrin, immunofluorescence, molecular docking
Full Text:
PDFReferences
Baldwin, A.S. Jr, 2001, Series Introduction: the Transcription Factor NF-kappaB and Human Disease, J. Clin. Investig.,
107(1), 3–6. CrossRef
Dean, M., Rzhetsky, A. and Allikmets, R., 2001, The Human ATP-Binding Cassette (ABC) Transporter Superfamily, Genome Res., 11(7), 1156-1166. CrossRef
Departemen Kesehatan RI, 2006, Gaya Hidup Penyebab Kolorektal,
e mid=2, Cited September 20, 2014.
DeVita, V.T., Theodore,, S.L. and Steven A.R., 2011, Cancer Principles and Practice of Oncology, 9th edition, Philadelphia: Wolters Kluwer, Lippinot Williams and Wilkins. Link
Dey, P. and Chaudhuri, T.K., 2014, Pharmacological Aspects of Nerium indicum Mill: A Comprehensive Review.,
Pharmacogn. Rev., 8(16), 156–162. CrossRef
Escárcega, R.O., Fuentes-Alexandro, S., García-Carrasco, M., Gatica, A. and Zamora, A., 2007, The Transcription Factor
Nuclear Factor-kB and Cancer, Clin. Oncol., 19(2), 154–161. Link
Ferlay, J., Shin, H.R., Bray, F., Forman, D., Mathers, C. and Parkin, D.M., 2010, Estimates of Worldwide Burden of Cancer 2008, Int. J. Cancer, 127(12), 2893-2917. CrossRef
Ghosh, S. and Hayden, M.S., 2008, New Regulators of NF-κB in Inflammation., Nat. Rev. Immunol., 8(11), 837-848. CrossRef
Giardina, C. and Hubbard, A.K., 2002. Growing Old with Nuclear FactorkappaB, Cell Stress Chaperones, 7(2),
–212. Link
Juliano, R.L. and Ling, V., 1976, A Surface Glycoprotein Modulating Drug Permeability in Chinese Hamster Ovary Cell Mutants, Biochim. Biophys. Acta., 455(1), 152–162. Link
Kim, H.J., Hawke, N Baldwin, AS. NF-kappaB and IKK as
Therapeutic Targets in Cancer, Cell Death Differ., 13(5), 738-747. CrossRef
Krishna, R. and Mayer,L.D., 2000, Multidrug Resistance (MDR) in Cancer Mechanisms, Reversal Using Modulators of MDR and the Role of MDR Modulators in Influencing the Pharmacokinetics of Anticancer Drugs 11(4), 265-283. Link
Li,FY, Lai, MD. 2009. Colorectal Cancer, One Entity or Three, J. Zhejang Univ. Sci., 10(3),219-229. CrossRef
Meyerhardt, J.A. and Mayer, R.J., 2005, Therapy for Colorectal Cancer, N. Engl. J. Med., 352(5), 476-487. CrossRef
Newman, R.A., Kondo, Y., Yokoyama, T., Dixon S., Cartwright C., Chan, D., et al., 2007, Autophagic Cell Death of Human Pancreatic Tumor Cells Mediated by Oleandrin, a Lipidsoluble Cardiac Glycoside, Integr. Cancer Ther., 6(4), 354–364. CrossRef
Pratt, S., Shepard, R.L., Kandasamy, R.A., Johnston, P.A., Perry, W. III. and Dantzig, A.H., 2005, The Multidrug Resistance Protein 5 (ABCC5) Confers Resistance to 5-fluorouracil and Transports its Monophosphorylated Metabolites, Mol. Cancer Ther., 4(5), 855-863. CrossRef
Thévenod, F., Friedmann, J.M., Katsen, A.D. and Hauser, I.A., 2000, Up-regulation of Multidrug Resistance P-glycoprotein via Nuclear Factor-kappa B Activation Protects Kidney Proximal Tubule Cells from Cadmium and Reactive Oxygen Species-induced Apoptosis, J. Biol. Chem., 275(3), 1887–1896. Link
Thu, Y.M. and Richmond, A., 2010, NF- kB Inducing Kinase: A Key Regulator in the Immune System and Cancer, Cytokine Growth Factor Rev., 21(4), 213-226. CrossRef
Verma, I.M., 2004, Nuclear Factor (NF)-kappa B Proteins: Therapeutic Targets. Ann. Rheum. Dis., 63(2), 1157-1161. CrossRef
Voorhees, P.M., Dees, E.C., O’Neil, B. and Orlowski, R.Z., 2003, The Proteasome as a Target for Cancer Therapy, Clin. Cancer Res., 9(17), 6316-6325. Link
Zibbu, G. and Batra, A., 2010, A Review on Chemistry and Pharmacological activity of Nerium oleander L., J. Chem. Pharm. Res., 2(6), 351-358. Link
DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev7iss3pp87-92
Copyright (c) 2017 Indonesian Journal of Cancer Chemoprevention
Indexed by:
Indonesian Society for Cancer Chemoprevention
