Assessment of in vitro antitumor potential of luteolin loaded polymeric nanofromulations

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Research Paper 01/11/2018
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Assessment of in vitro antitumor potential of luteolin loaded polymeric nanofromulations

Umara Afzal, Muhammad Gulfraz, S.M. Saqlan Naqvi, Nadeem Akhtar Abbasi, Muhammad Awais, Warda Ahmad, Salma Batool
Int. J. Biosci.13( 5), 195-204, November 2018.
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Abstract

Non-small cell lung cancer (NSCLC) is one of the fetal type of lung cancer worldwide with high resistant against current chemotherapeutic agents due to increase their aggressive features. Many plant derived natural compounds have been found to possess antimetastatic potential against NSCLC by inhibiting molecular product and correspondingly their growth. Luteolin is plant derived flavonoid with potential antioxidant, anti-inflammatory and anticancer potential against multiple malignancies but its bioavailability is low due to hydrophobic nature with less half-life. Current study was designed to increase bioavailability of luteolin by formulate in physiologically stable and biodegradable polymer Poly (lactic-co-glycolic) acid. Surface modified PLGA with PEG (PEG-PLGA NPs) was used as comparative formulation. Both formulations were made by single emulsion method. Physiochemical characteristics including surface morphology, size and charge and stability in NaCl and serum medium was done for both formulations. Invitro antitumor potential of free and formulated luteolin against Non-small cell lung cancer (NSCLC) was done using CCK-8 assay and % viability was determined. Results from physiochemical characterization showed 156nm particles of PEG-PLGA and slightly large 350nm sized particles of PLGA suspended in PBS whereas TEM images showed <100nm sized PEGylated NPs with high payload of luteolin drug with sustained release up to two days as determined by HPLC analysis. Invitro tumor growth inhibition assay showed cytotoxic potential of nanofromulation of luteolin as compared to free luteolin. Results of both PLGA and PEG-PLGA formulations of luteolin showed promising potential for further in vivo therapeutic approach against NSCLC.

VIEWS 16

American Cancer Society. 2015. Cancer Facts & Figures 2015. Atlanta, GA: American Cancer Society, 1–9.

Amin AR, Wang D, Zhang H, Peng S, Shin HJ, Brandes JC, Mourad T, Fadlo R, Zhuo GC, Dong MS. 2010. Enhanced anti-tumor activity by the combination of the natural compounds (-)-epigallocatechin-3-gallate and luteolin: potential role of p53. Journal of Biological Chemistry 285, 34557. https://doi.org/10.1074/jbc.M110.141135

Cai X, Ye T, Liu C, Lu W, Lu M, Zhang J. 2011. Luteolin induced G2 phase cell cycle arrest and apoptosis on non-small cell lung cancer cells. Toxicology In Vitro 25, 1385–91. https://doi.org/10.1016/j.tiv.2011.05.009

Ding S, Hu A, Hu Y, Ma J, Weng P, Dai J. 2014. Anti-hepatoma cells function of luteolin through inducing apoptosis and cell cycle arrest. Tumor Biology 35(4), 3053–60. https://doi.org/10.1007/s13277-013-1396-5

Huang CY, Ju DT, Chang CF, Muralidhar Reddy P, Velmurugan BK. 2017.  A review on the effects of current chemotherapy drugs and natural agents in treating non–small cell lung cancer. Biomedicine 7(4), 23-29. https://doi.org/10.1051/bmdcn/2017070423

Jemal  A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. 2007 Cancer statistics,2007. CA Cancer Journal of Clinicians 57, 43-66.

Ju W, Wang X, Shi H, Chen W, Belinsky SA, Lin Y. 2007. A critical role of luteolin-induced reactive oxygen species in blockage of tumor necrosis factor-activated NF-kB pathway and sensitization of apoptosis in lung cancer cells. Molecular Pharmacology 71, 1381–1388. https://doi.org/10.1124/mol.106.032185

Kandaswami C, Lee LT, Lee PP, Hwang JJ, Ke FC, Huang YT. 2005. The antitumor activities of flavonoids. In Vivo 19, 895–909.

Kim YA, Yu JG, Lee KW, Lee HJ. 2013. Luteolin suppresses UVB-induced photoageing by targeting JNK1 and p90 RSK2. Journal of Cellular and Molecular Medicine 17(5), 672–80. https://doi.org/10.1111/jcmm.12050

Kumari A, Yadav SK, Yadav SC. 2010. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids and Surfaces B: Bio interfaces 75(1), 1–18. https://doi.org/10.1016/j.colsurfb.2009.09.001

Lee HZ, Yang WH, Bao BY, Lo PL. 2010. Proteomic analysis reveals ATP dependent steps and chaperones involvement in luteolin-induced lung cancer CH27 cell apoptosis. European Journal of Pharmacology 642(1-3), 19–27. https://doi.org/10.1016/j.ejphar.2010.05.053

Lim do Y, Jeong Y, Tyner AL, Park JH. 2007. Induction of cell cycle arrest and apoptosis in HT-29 human colon cancer cells by the dietary compound luteolin. American Journal of Physiology: Gastrointestinal and Liver Physiology 292, 66–75. https://doi.org/10.1152/ajpgi.00248.2006

Lin Y, Shi R, Wang X, Shen HM. 2008. Luteolin. A flavonoid with potential for cancer prevention and therapy. Current Cancer Drug Targets 8, 634–46.

Majumdar D, Jung KH, Zhang H,  Nannapaneni S, Wang X, Amin AR, Chen Z, Chen ZG, Shin DM. 2014. Luteolin nanoparticle in chemoprevention: in vitro and in vivo anticancer activity. Cancer Prevention Research. 7(1), 65-73. https://doi.org/10.1158/1940-6207.CAPR-13-0230

Molina JR, Yang P, Cassivi S D, Schild SE, Adjei A. 2008. Non-small cell lung cancer: Epidemiology, Risk Factors, Treatment, and survivorship. Mayo Clinical Procedures 83(5), 584–594. https://doi.org/10.4065/83.5.584

Nance EA, Woodworth GF, Sailor, KA, Shih, TY, Xu Q, Swaminathan G, Dennis X, Charles E, Hanes J. 2012. A Dense Poly(Ethylene Glycol) Coating Improves Penetration of Large Polymeric Nanoparticles Within Brain Tissue. Science Translational Medicine 4(149), 149ra119. https://doi.org/10.1126/scitranslmed.3003594

Ong CS, Zhou J, Ong CN, Shen HM. 2010. Luteolin induces G1 arrest in human nasopharyngeal carcinoma cells via the Akt-GSK-3b-cyclin D1 pathway. Cancer Letters 298, 167–75. https://doi.org/10.1016/j.canlet.2010.07.001

Pithi C, Supakarn C, Chuanpit N, Preeyaporn PP. 2016. Potential Anti-metastasis Natural Compounds for Lung Cancer. Anticancer Research. 36(11), 5707-5717. https://doi.org/10.21873/anticanres.11154

Sahu A, Bora U, Kasoju N, Goswami P. 2008. Synthesis of novel biodegradable and self-assembling methoxy poly(ethylene glycol)–palmitate nanocarrier for curcumin delivery to cancer cells. Acta Biomaterialia 4(6), 1752–1761. https://doi.org/10.1016/j.actbio.2008.04.021

Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J. 2002. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346, 92-8.

Siddiqui IA, Adhami VM, Bharali DJ, Hafeez BB, Asim M, Khwaja SI, Mukhtar H. 2009. Introducing Nanochemoprevention as a Novel Approach for Cancer Control: Proof of Principle with Green Tea Polyphenol Epigallocatechin-3-Gallate. Cancer Research 69(5), 1712–1716. https://doi.org/10.1158/0008-5472.CAN-08-3978

Van Meerbeeck JP, Fennell DA, De Ruysscher DK. 2011. Small-cell lung cancer. The Lancet 378(9804), 1741–1755. https://doi.org/10.1016/S0140-6736(11)60165-7

Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C. 2005. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 352, 2589-97. https://doi.org/10.1056/NEJMoa043623

Yang SF, Yang WE, Chang HR, Chu SC, Hsieh YS. 2008. Luteolin induces apoptosis in oral squamous cancer cells. Journal of Dental Research; 87, 401–6. https://doi.org/10.1177/154405910808700413

Zhang Q, Zhao XH, Wang ZJ. 2008. Flavones and flavonols exert cytotoxic effects on a human oesophageal adenocarcinoma cell line (OE33) by causing G2/M arrest and inducing apoptosis. Food Chemistry and Toxicology 46, 2042–53. https://doi.org/10.1016/j.fct.2008.01.049