Improved Drug Delivery System for Cancer Treatment by D-Glucose Conjugation with Eugenol From Natural Product

Author(s): Mas Amira Idayu Abdul Razak, Haslinda Abdul Hamid, Raja Nor Izawati Raja Othman, Shaik Alaudeen Mohd Moktar, Azizi Miskon*

Journal Name: Current Drug Delivery

Volume 18 , Issue 3 , 2021


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Introduction: Bioconjugations are swiftly progressing and are being applied to solve several limitations of conventional Drug Delivery Systems (DDS) such as lack of water solubility, non-specific, and poor bioavailability. The main goals of DDS are to achieve greater drug effectiveness and minimize toxicity to the healthy tissues.

Objectives and Methods: In this study, D-glucose was conjugated with eugenol to target the cancer cells. To identify the implication of the anticancer effect, osteosarcoma (K7M2) cells were cultured and the anti-proliferative effect was performed using MTT [3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide assay] test in order to evaluate the viability and toxicity on cells with various concentrations of eugenol and D-glucose-eugenol conjugate in 24-hour incubation.

Results: It was found that, the successful confirmation of the conjugation between D-glucose and eugenol was obtained by 1H NMR spectroscopy. MTT assay showed inhibitory concentration (IC50 value) of D-glucose-eugenol was at 96.2 μg/ml and the decreased of osteosarcoma cell survival was 48%.

Conclucion: These findings strongly indicate that K7M2 cells would be affected by toxicity of Dglucose- eugenol. Therefore, the present study suggests that D-glucose-eugenol has high potential to act as an anti-proliferative agent who may promise a new modality or approach as the drug delivery treatment for cancer or chemotherapeutic agent.

Keywords: Conjugation, D-glucose, eugenol, Drug Delivery Systems (DDS), cancer treatment, osteosarcoma (K7M2).

[1]
American cancer society. Cancer facts & figures 2016. Cancer Facts Fig., 2016, 2016, 1-9.
[2]
Wild, C.P. The global cancer burden: necessity is the mother of prevention. Nat. Rev. Cancer, 2019, 19(3), 123-124.
[http://dx.doi.org/10.1038/s41568-019-0110-3] [PMID: 30683893]
[3]
Debele, T.A.; Mekuria, S.L.; Tsai, H. Polysaccharide based nanogels in the drug delivery system: Application as the carrier of pharmaceutical agents. Mater. Sci. Eng. C Mater. Biol. Appl., 2016, 68, 964-981.
[4]
Granchi, C.; Fancelli, D.; Minutolo, F. An update on therapeutic opportunities offered by cancer glycolytic metabolism. Bioorg. Med. Chem. Lett., 2014, 24(21), 4915-4925.
[http://dx.doi.org/10.1016/j.bmcl.2014.09.041] [PMID: 25288186]
[5]
Gomis, R.R. Survival skills ensure that cancer spreads. Nature, 2019, 573(7774), 353-354.
[http://dx.doi.org/10.1038/d41586-019-02570-z] [PMID: 31530905]
[6]
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: the next generation. Cell, 2011, 144(5), 646-674.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[7]
Vijaya, S.; Sudhakar, Y.; Venkateswarlu, B. Current review on organophosphorus poisoning. Arch. Appl. Sci. Res., 2010, 2(4), 199-215.
[8]
Mortezaee, K. Modulation of apoptosis by melatonin for improving cancer treatment efficiency : an updated review. Life Sci., 2019, 228, 228-241.
[9]
Reddy, P.D.; Swarnalatha, D. Recent advances in novel drug delivery systems. J. Materials, 2010, 2(3), 2025-2027.
[10]
Miskon, A.; Ibrahim, N.; Mohd Tawil, S.N. A model of Defence mechanical Drug delivery system (DmechD) and the drug release efficacy IECBES 2014.Conf. Proc. - 2014 IEEE Conf. Biomed. Eng. Sci. “Miri, Where Eng. Med. Biol. Humanit. Meet, 2015, pp. 22-26.
[11]
Devi, V.K.; Jain, N.; Valli, K.S. Importance of novel drug delivery systems in herbal medicines. Pharmacogn. Rev., 2010, 4(7), 27-31.
[http://dx.doi.org/10.4103/0973-7847.65322] [PMID: 22228938]
[12]
Saini, R.K.; Chouhan, R.; Bagri, L.P.; Bajpai, A.K. Strategies of targeting tumors and cancers. J. Cancer Res. Updates, 2012, 1(1), 129-152.
[13]
Anselmo, A.C.; Mitragotri, S. An overview of clinical and commercial impact of drug delivery systems. J. Control. Release, 2014, 190, 15-28.
[http://dx.doi.org/10.1016/j.jconrel.2014.03.053] [PMID: 24747160]
[14]
Gothoskar, A.V.; Joshi, A.M. Drug delivery systems: an updated review. Int. J. Pharm. Investig., 2012, 2(1), 2-11.
[15]
Ricart, A.D. Drug-delivery systems in cancer therapy. Signal Transduct. Target. Therapy., 2018, 3, 7.
[16]
Hossen, S.; Hossain, M.K.; Basher, M.K.; Mia, M.N.H.; Rahman, M.T.; Uddin, M.J. Smart nanocarrier-based drug delivery systems for cancer therapy and toxicity studies: a review. J. Adv. Res., 2018, 15, 1-18.
[http://dx.doi.org/10.1016/j.jare.2018.06.005] [PMID: 30581608]
[17]
Faiz Norrrahim, M.N. Recent developments on oximes to improve the blood brain barrier penetration for the treatment of organophosphorus poisoning: a review. RSC Adv., 2020, 10(8), 4465-4489.
[http://dx.doi.org/10.1039/C9RA08599H]
[18]
Shahriari, M.; Zahiri, M.; Abnous, K.; Taghdisi, S.M.; Ramezani, M.; Alibolandi, M. Enzyme responsive drug delivery systems in cancer treatment. J. Control. Release, 2019, 308, 172-189.
[http://dx.doi.org/10.1016/j.jconrel.2019.07.004] [PMID: 31295542]
[19]
Calvo, B.; Pulido, E.G. Potential role of sugar transporters in cancer and their relationship with anticancer therapy. Int. J. Endocrinol., 2010, Article ID 205357.
[20]
Pastuch-Gawołek, G.; Malarz, K.; Mrozek-Wilczkiewicz, A.; Musioł, M.; Serda, M.; Czaplinska, B.; Musiol, R. Small molecule glycoconjugates with anticancer activity. Eur. J. Med. Chem., 2016, 112, 130-144.
[http://dx.doi.org/10.1016/j.ejmech.2016.01.061] [PMID: 26890119]
[21]
Ferreira, L.M.R. Cancer metabolism: the Warburg effect today. Exp. Mol. Pathol., 2010, 89(3), 372-380.
[http://dx.doi.org/10.1016/j.yexmp.2010.08.006] [PMID: 20804748]
[22]
Tateishi, U.; Miyake, M.; Nagaoka, T.; Terauchi, T.; Kubota, K.; Kinoshita, T.; Daisaki, H.; Macapinlac, H.A. Neoadjuvant chemotherapy in breast cancer: prediction of pathologic response with PET/CT and dynamic contrast-enhanced MR imaging--prospective assessment. Radiology, 2012, 263(1), 53-63.
[http://dx.doi.org/10.1148/radiol.12111177] [PMID: 22438441]
[23]
Currie, C.J.; Poole, C.D.; Gale, E.A.M. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia, 2009, 52(9), 1766-1777.
[24]
Macheda, M.L.; Rogers, S.; Best, J.D. Molecular And Cellular Regulation Of Glucose Transporter (GLUT) proteins in cancer. J. Cell. Physiol., 2005, 202(3), 654-662.
[http://dx.doi.org/10.1002/jcp.20166] [PMID: 15389572]
[25]
Krzeslak, A.; Wojcik-Krowiranda, K.; Forma, E.; Jozwiak, P.; Romanowicz, H.; Bienkiewicz, A.; Brys, M. Expression of GLUT1 and GLUT3 glucose transporters in endometrial and breast cancers. Pathol. Oncol. Res., 2012, 18(3), 721-728.
[http://dx.doi.org/10.1007/s12253-012-9500-5] [PMID: 22270867]
[26]
Li, L.; Kang, L.; Zhao, W.; Feng, Y.; Liu, W.; Wang, T.; Mai, H.; Huang, J.; Chen, S.; Liang, Y.; Han, J.; Xu, X.; Ye, Q. miR-30a-5p suppresses breast tumor growth and metastasis through inhibition of LDHA-mediated Warburg effect. Cancer Lett., 2017, 400, 89-98.
[http://dx.doi.org/10.1016/j.canlet.2017.04.034] [PMID: 28461244]
[27]
Sztandera, K.; Dzia, P.; Marcinkowska, M.; Sta, M. Sugar modification enhances cytotoxic activity of PAMAM-doxorubicin conjugate in glucose-deprived MCF-7 cells – possible role of GLUT1 transporter. Pharm. Res., 2019, 36(10), 140.
[28]
Seyfried, T.N.; Huysentruyt, L.C. On the origin of cancer metastasis. Crit. Rev. Oncog., 2013, 18(1-2), 43-73.
[http://dx.doi.org/10.1615/CritRevOncog.v18.i1-2.40] [PMID: 23237552]
[29]
Calvaresi, E.C.; Hergenrother, P.J. Glucose conjugation for the specific targeting and treatment of cancer. Chem. Sci. (Camb.), 2013, 4(6), 2319-2333.
[http://dx.doi.org/10.1039/c3sc22205e] [PMID: 24077675]
[30]
Amann, T.; Maegdefrau, U.; Hartmann, A.; Agaimy, A.; Marienhagen, J.; Weiss, T.S.; Stoeltzing, O.; Warnecke, C.; Schölmerich, J.; Oefner, P.J.; Kreutz, M.; Bosserhoff, A.K.; Hellerbrand, C. GLUT1 expression is increased in hepatocellular carcinoma and promotes tumorigenesis. Am. J. Pathol., 2009, 174(4), 1544-1552.
[http://dx.doi.org/10.2353/ajpath.2009.080596] [PMID: 19286567]
[31]
Patra, M.; Johnstone, T.C.; Suntharalingam, K.; Lippard, S.J. Medicinal inorganic chemistry A potent glucose – platinum conjugate exploits glucose transporters and preferentially accumulates in cancer cells. Angew. Chem. Int. Ed. Engl., 2016, 55(7), pp. 2550-2554.
[32]
Tanaka, M.; Kataoka, H.; Yano, S.; Ohi, H.; Kawamoto, K.; Shibahara, T.; Mizoshita, T.; Mori, Y.; Tanida, S.; Kamiya, T.; Joh, T. Anti-cancer effects of newly developed chemotherapeutic agent, glycoconjugated palladium (II) complex, against cisplatin-resistant gastric cancer cells. BMC Cancer, 2013, 13(1), 237.
[http://dx.doi.org/10.1186/1471-2407-13-237] [PMID: 23672493]
[33]
Li, H.; Gao, X.; Liu, R.; Wang, Y.; Zhang, M.; Fu, Z.; Mi, Y.; Wang, Y.; Yao, Z.; Gao, Q. A potent glucose – platinum conjugate exploits glucose transporters and preferentially accumulates in cancer cells. Angewandte, 2015, 2550-2554.
[34]
Granchi, C.; Fortunato, S.; Minutolo, F. Anticancer agents interacting with membrane glucose transporters. MedChemComm, 2016, 7(9), 1716-1729.
[http://dx.doi.org/10.1039/C6MD00287K] [PMID: 28042452]
[35]
Pourcel, L.; Routaboul, J.M.; Cheynier, V.; Lepiniec, L.; Debeaujon, I. Flavonoid oxidation in plants: from biochemical properties to physiological functions. Trends Plant Sci., 2007, 12(1), 29-36.
[http://dx.doi.org/10.1016/j.tplants.2006.11.006] [PMID: 17161643]
[36]
Kashyap, D.; Tuli, H.S.; Yerer, M.B. Natural product-based nanoformulations for cancer therapy: opportunities and challenges. Seminars. Cancer Biol., 2019. Epub ahead of print
[37]
Ghosh, R.; Nadiminty, N.; Fitzpatrick, J.E.; Alworth, W.L.; Slaga, T.J.; Kumar, A.P. Eugenol causes melanoma growth suppression through inhibition of E2F1 transcriptional activity. J. Biol. Chem., 2005, 280(7), 5812-5819.
[http://dx.doi.org/10.1074/jbc.M411429200] [PMID: 15574415]
[38]
Choudhury, P.; Barua, A.; Roy, A.; Pattanayak, R.; Bhattacharyya, M.; Saha, P. Eugenol restricts cancer stem cell population by degradation of β-catenin via N-terminal Ser37 phosphorylation-an i n vivo and in vitro experimental evaluation. Chem. Biol. Interact., 2020, 316, 108938.
[http://dx.doi.org/10.1016/j.cbi.2020.108938] [PMID: 31926151]
[39]
Hemaiswarya, S.; Doble, M. Synergistic interaction of phenylpropanoids with antibiotics against bacteria. J. Med. Microbiol., 2010, 59(Pt 12), 1469-1476.
[http://dx.doi.org/10.1099/jmm.0.022426-0] [PMID: 20724513]
[40]
Pramod, K.; Ansari, S.H.; Ali, J. Eugenol: a natural compound with versatile pharmacological actions. Nat. Prod. Commun., 2010, 5(12), 1999-2006.
[http://dx.doi.org/10.1177/1934578X1000501236] [PMID: 21299140]
[41]
Lanzillotto, M.; Konnert, L.; Lamaty, F.; Martinez, J.; Colacino, E. Mechanochemical 1,1′-carbonyldiimidazole-mediated synthesis of carbamates. ACS Sustain. Chem.& Eng., 2015, 3(11), 2882-2889.
[http://dx.doi.org/10.1021/acssuschemeng.5b00819]
[42]
Thorpe, C.; Epple, S.; Woods, B.; El-Sagheer, A.H.; Brown, T. Synthesis and biophysical properties of carbamate-Locked Nucleic Acid (LNA) oligonucleotides with potential antisense applications. Org. Biomol. Chem., 2019, 17(21), 5341-5348.
[http://dx.doi.org/10.1039/C9OB00691E] [PMID: 31099373]
[43]
Montalbetti, C.A.G.N.; Falque, V. Amide bond formation and peptide coupling. Tetrahedron, 2005, 61(46), 10827-10852.
[http://dx.doi.org/10.1016/j.tet.2005.08.031]
[44]
Woodman, E.K.; Chaffey, J.G.K.; Hopes, P.A.; Hose, D.R.J.; Gilday, J.P. N,N′-carbonyldiimidazole-mediated amide coupling : significant rate enhancement achieved by acid catalysis with imidazole • HCl. Org. Process Res. Dev., 2009, 6, 106-113.
[45]
Onche, E.U.; Tukura, B.W.; Bako, S.S. Nuclear Magnetic Resonance (NMR) analysis of D - (+) - Glucose: a guide to spectrometric structural elucidation of sugars. IOSR J. Appl. Chem., 2013, 6(1), 45-51.
[http://dx.doi.org/10.9790/5736-0614551]
[46]
Hu, P.; Ben-David, Y.; Milstein, D. Rechargeable hydrogen storage system based on the dehydrogenative coupling of ethylenediamine with ethanol. Angew. Chem. Int. Ed. Engl., 2016, 55(3), 1061-1064.
[http://dx.doi.org/10.1002/anie.201505704] [PMID: 26211515]
[47]
Cary, R. 1,2-diaminoethane (ethylenediamine). World Health Org., 1999, 27-28.
[48]
Katritzky, A.R.; Monbaliu, J.C.M. The chemistry of benzotriazole derivatives: a tribute to Alan Roy Katritzky. Topics Heterocyclic Chem., 2016, 43(43), 300.
[49]
Ghosh, A.K.; Brindisi, M. Organic carbamates in drug design and medicinal chemistry. J. Med. Chem., 2015, 58(7), 2895-2940.
[http://dx.doi.org/10.1021/jm501371s] [PMID: 25565044]
[50]
Reich, H.J. 5.2 Chemical shift; structure determination using spectroscopy. Methods, 2014, pp. 1-23.
[51]
Gurst, J.E. NMR and the structure of D-glucose. Textb. Forum, 1991, 68(12), 1003-1004.
[http://dx.doi.org/10.1021/ed068p1003]
[52]
Ikeda, R.; Uyama, H.; Kobayashi, S. Novel synthetic pathway to a poly(phenylene oxide). laccase-catalyzed oxidative polymerization of syringic acid, no. Scheme, 1996, 1, 3053-3054.
[http://dx.doi.org/10.1021/ma951810b]
[53]
Meng, S.; Cao, J.; Feng, Q.; Peng, J.; Hu, Y. Roles of chlorogenic acid on regulating glucose and lipids metabolism: a review. Evid. Based Complement. Alternat. Med., 2013, 2013, 22.
[54]
Chen, L.; Teng, H.; Cao, H. Chlorogenic acid and caffeic acid from Sonchus oleraceus Linn synergistically attenuate insulin resistance and modulate glucose uptake in HepG2 cells. Food Chem. Toxicol., 2019, 127, 182-187.
[http://dx.doi.org/10.1016/j.fct.2019.03.038] [PMID: 30914352]
[55]
Bagno, A.; Rastrelli, F.; Saielli, G. Prediction of the 1 H and 13 C NMR spectra of r - D -glucose in water by DFT methods and MD simulations. The J. Phys. Chem. A, 2007, pp. 7373-7381.
[56]
Vidhya, N.; Devaraj, S.N. Induction of apoptosis by eugenol in human breast cancer cells. Indian J. Exp. Biol., 2011, 49, 871-878.
[57]
Baharara, J.; Ramezani, T.; Mousavi, M.; Kouhestanian, K. Eugenol suppressed metastasis of breast carcinoma cells and migration by regulation of MMP-9 & paxilin gene expression. Sch. J. Agric. Vet. Sci., 2015, 2(2B), 125-130.
[58]
Fisher, R.A. The use of multiple measurements in taxonomic problems. Annals Eugenics, 1954, 1(1), 1-8.
[59]
Rothstein, E.L.; Hartzell, R.W., Jr; Manson, L.A.; Kritchevsky, D. Effects of D2O on cellular components of mammalian cells grown in tissue culture. Ann. NY. Acad. Sci., 1960, 84(16), 721-726.
[http://dx.doi.org/10.1111/j.1749-6632.1960.tb39103.x] [PMID: 13743911]
[60]
Takeda, H.; Nio, Y.; Omori, H.; Uegaki, K.; Hirahara, N.; Sasaki, S.; Tamura, K.; Ohtani, H. Mechanisms of cytotoxic effects of heavy water (deuterium oxide: D2O) on cancer cells. Anticancer Drugs, 1998, 9(8), 715-725.
[http://dx.doi.org/10.1097/00001813-199809000-00007] [PMID: 9823430]
[61]
Patra, M.; Awuah, S.G.; Lippard, S.J. Chemical approach to positional isomers of glucose-platinum conjugates reveals specific cancer targeting through glucose-transporter-mediated uptake in vitro and in vivo . J. Am. Chem. Soc., 2016, 138(38), 12541-12551.
[http://dx.doi.org/10.1021/jacs.6b06937] [PMID: 27570149]
[62]
Sanae, F.; Kamiyama, O.; Ikeda-Obatake, K.; Higashi, Y.; Asano, N.; Adachi, I.; Kato, A. Effects of eugenol-reduced clove extract on glycogen phosphorylase b and the development of diabetes in db/db mice. Food Funct., 2014, 5(2), 214-219.
[http://dx.doi.org/10.1039/C3FO60514K] [PMID: 24336787]
[63]
Singh, R.; Barden, A.; Mori, T.; Beilin, L. Advanced glycation end-products: a review. Diabetologia, 2001, 44(2), 129-146.
[http://dx.doi.org/10.1007/s001250051591] [PMID: 11270668]
[64]
Alphey, M.S.; Pirrie, L.; Torrie, L.S.; Boulkeroua, W.A.; Gardiner, M.; Sarkar, A.; Maringer, M.; Oehlmann, W.; Brenk, R.; Scherman, M.S.; McNeil, M.; Rejzek, M.; Field, R.A.; Singh, M.; Gray, D.; Westwood, N.J.; Naismith, J.H. Allosteric competitive inhibitors of the glucose-1-phosphate thymidylyltransferase (RmlA) from Pseudomonas aeruginosa . ACS Chem. Biol., 2013, 8(2), 387-396.
[http://dx.doi.org/10.1021/cb300426u] [PMID: 23138692]
[65]
Jaganathan, S.K.; Supriyanto, E. Antiproliferative and molecular mechanism of eugenol-induced apoptosis in cancer cells. Molecules, 2012, 17(6), 6290-6304.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 18
ISSUE: 3
Year: 2021
Published on: 17 September, 2020
Page: [312 - 322]
Pages: 11
DOI: 10.2174/1567201817666200917123639
Price: $65

Article Metrics

PDF: 23
HTML: 2