Abstract
White tea (WT) has the highest amount of catechin which previously was found to enhance anti-cancer activity. To enhance the bioavailability of WT, silver nanoparticle (AgNP) was used to synthesize WT nanoparticle (WTNP). This present study aimed to determine the effectiveness of WTNP alone and co-administered with 5FU in the prophylactic study. WTNP was characterized by UV–Vis spectra, X-ray diffraction (XRD) spectra, transmission electron microscope (TEM) and Fourier-transform infrared spectroscopy (FTIR) and tested for their acute toxicity. In animal studies, all groups except the naïve group were given once a week 65 mg/kg of 1,2-dimethylhydrazine (DMH) subcutaneously, intraperitoneal injection of 50 mg/kg 5FU and daily administration of DMH 50 mg/kg WT and 5FU WTNPs. Aberrant crypt foci (ACF) and histology were determined and analysed. WTNP showed circular and pseudospherical shaped and 25–50 nm size range with no acute toxicity observed on rats. The DMH group was the highest in average ACF count (37.3 ± 3.18), which ACF was shown to decrease using the treatment, WT group (16.67 ± 3.28), 5FU monotherapy (5.67 ± 2.19) and WTFU (6.33 ± 1.33). The highest AC frequency was found at the DMH group (24.67 ± 1.20, 12.67 ± 1.45) compared to other groups. The chemo-suppressive effect of WTNP and WTFU combined effects was observed in the present study. WTNP expresses anti-cancer properties; however, it does not produce any synergistic effect.
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References
Keum, N., & Giovannucci, E. (2019). Global burden of colorectal cancer: Emerging trends, risk factors and prevention strategies. Nature Reviews Gastroenterology & Hepatology, 16(12), 713–732. https://doi.org/10.1038/s41575-019-0189-8
Marley, A. R., & Nan, H. (2016). Epidemiology of colorectal cancer. International journal of molecular epidemiology and genetics, 7(3), 105–114.
Krohe, M., Eek, D., Mazar, I., Horsfield, A., Pompilus, F., Friebe, R., & Shields, A. (2016). Patient-reported preferences for oral versus intravenous administration for the treatment of cancer: A review of the literature. Patient Preference and Adherence, 10, 1609–1621. https://doi.org/10.2147/PPA.S106629
Gelperina, S., Kisich, K., Iseman, M. D., & Heifets, L. (2005). The potential advantages of nanoparticle drug delivery systems in chemotherapy of tuberculosis. American Journal of Respiratory and Critical Care Medicine, 172(12), 1487–1490. https://doi.org/10.1164/rccm.200504-613PP
Sanlier, N., Atik, İ, & Atik, A. (2018). A minireview of effects of white tea consumption on diseases. Trends in Food Science and Technology, 82(September), 82–88. https://doi.org/10.1016/j.tifs.2018.10.004
Hilal, Y., & Engelhardt, U. (2007). Characterisation of white tea - Comparison to green and black tea. Journal fur Verbraucherschutz und Lebensmittelsicherheit, 2(4), 414–421. https://doi.org/10.1007/s00003-007-0250-3
Qiao, J., Kong, X., Kong, A., & Han, M. (2014). Pharmacokinetics and biotransformation of tea polyphenols. Current Drug Metabolism, 15(1), 30–36. https://doi.org/10.2174/1389200214666131229111336
Gong, R., & Chen, G. (2016). Preparation and application of functionalized nano drug carriers. Saudi Pharmaceutical Journal, 24(3), 254–257. https://doi.org/10.1016/j.jsps.2016.04.010
Gwinn, M. R., & Vallyathan, V. (2006). Nanoparticles: Health effects - Pros and cons. Environmental Health Perspectives, 114(12), 1818–1825. https://doi.org/10.1289/ehp.8871
Pitaksuteepong, T. (2016). Nanotechnology: Effective topical delivery systems. Asian Journal of Pharmaceutical Sciences, 11(1), 16–17. https://doi.org/10.1016/j.ajps.2015.10.012
Kim, S., Choi, J. E., Choi, J., Chung, K. H., Park, K., Yi, J., & Ryu, D. Y. (2009). Oxidative stress-dependent toxicity of silver nanoparticles in human hepatoma cells. Toxicology in Vitro, 23(6), 1076–1084. https://doi.org/10.1016/j.tiv.2009.06.001
Rajawar, S., Kurchania, R., Rajakumar, K., Pitale, S., Saha, S., & Qureshi, M. S. (2016). Study of anti-cancer properties of green silver nanoparticles against MCF-7 breast cancer cell lines. Green Processing and Synthesis, 4(5), 399–410. https://doi.org/10.1515/gps-2015-0104
Haghparasti, Z., & Mahdavi Shahri, M. (2018). Green synthesis of water-soluble nontoxic inorganic polymer nanocomposites containing silver nanoparticles using white tea extract and assessment of their in vitro antioxidant and cytotoxicity activities. Materials Science and Engineering C, 87(2017), 139–148. https://doi.org/10.1016/j.msec.2018.02.026
Elbossaty, W. F. (2017). Green tea as biological system for the synthesis of silver nanoparticles. Journal of Biotechnology & Biomaterials, 07(03), 3–7. https://doi.org/10.4172/2155-952X.1000269
Sanna, V., Lubinu, G., Madau, P., Pala, N., Nurra, S., Mariani, A., & Sechi, M. (2015). Polymeric nanoparticles encapsulating white tea extract for nutraceutical application. Journal of Agricultural and Food Chemistry, 63(7), 2026–2032. https://doi.org/10.1021/jf505850q
Cisterna, B. A., Kamaly, N., Choi, W. I., Tavakkoli, A., Farokhzad, O. C., & Vilos, C. (2016). Targeted nanoparticles for colorectal cancer. Nanomedicine, 11(18), 2443–2456. https://doi.org/10.2217/nnm-2016-0194
Chintala, L., Vaka, S., Baranda, J., & Williamson, S. K. (2011). Capecitabine versus 5-fluorouracil in colorectal cancer: Where are we now? Oncology Reviews, 5(2), 129–140. https://doi.org/10.1007/s12156-011-0074-3
Gelen, V., Şengül, E., Yıldırım, S., & Atila, G. (2018). The protective effects of naringin against 5-fluorouracil-induced hepatotoxicity and nephrotoxicity in rats. Iranian Journal of Basic Medical Sciences, 21(4), 404–410. https://doi.org/10.22038/ijbms.2018.27510.6714
He, J., Pei, L., Jiang, H., Yang, W., Chen, J., & Liang, H. (2017). Chemoresistance of colorectal cancer to 5-fluorouracil is associated with silencing of the BNIP3 gene through aberrant methylation. Journal of Cancer, 8(7), 1187–1196. https://doi.org/10.7150/jca.18171
Srimuangwong, K. (2012). Effects of hexahydrocurcumin in combination with 5-fluorouracil on dimethylhydrazine-induced colon cancer in rats. World Journal of Gastroenterology, 18(47), 6951. https://doi.org/10.3748/wjg.v18.i47.6951
Handali, S., Moghimipour, E., Rezaei, M., Ramezani, Z., & Dorkoosh, F. A. (2020). PHBV/PLGA nanoparticles for enhanced delivery of 5-fluorouracil as promising treatment of colon cancer. Pharmaceutical development and technology, 25(2), 206–218. https://doi.org/10.1080/10837450.2019.1684945
Smith, T., Affram, K., Bulumko, E., & Agyare, E. (2018). Evaluation of in-vitro cytotoxic effect of 5-FU loaded-chitosan nanoparticles against spheroid models. Journal of nature and science, 4(10). Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/30740523
Loo, Y. Y., Chieng, B. W., Nishibuchi, M., & Radu, S. (2012). Synthesis of silver nanoparticles by using tea leaf extract from Camellia sinensis. International Journal of Nanomedicine, 7, 4263–4267. https://doi.org/10.2147/IJN.S33344
Lim, Y., Rajabalaya, R., Lee, S., Tennakoon, K., Le, Q.-V., Idris, A., … David, S. (2016). Parasitic mistletoes of the genera Scurrula and Viscum: From bench to bedside. Molecules, 21(8), 1048. https://doi.org/10.3390/molecules21081048
Zulkipli, I., Rajabalaya, R., David, S., & Idris, A. (2015). Medicinal plants: A potential source of compounds for targeting cell division. Drug Target Insights, 9, 9–19. https://doi.org/10.4137/DTI.S24946
Happy, A., Soumya, M., Venkat Kumar, S., Rajeshkumar, S., Sheba, R. D., Lakshmi, T., & Deepak Nallaswamy, V. (2019). Phyto-assisted synthesis of zinc oxide nanoparticles using Cassia alata and its antibacterial activity against Escherichia coli. Biochemistry and Biophysics Reports, 17, 208–211. https://doi.org/10.1016/j.bbrep.2019.01.002
Zulkipli, I. N., Rajabalaya, R., Idris, A., Sulaiman, N. A., & David, S. R. (2017). Clinacanthus nutans : A review on ethnomedicinal uses, chemical constituents and pharmacological properties. Pharmaceutical Biology, 55(1), 1093–1113. https://doi.org/10.1080/13880209.2017.1288749
David, S. R., Refai, S. A., Yian, K. R., Mai, C. W., Das, S. K., & Rajabalaya, R. (2019). Development and evaluation of liquid crystal systems of combination of 5-fluorouracil and curcumin for cervical cancer cell line. Journal of Pharmacy and Pharmacognosy Research, 7(6), 441–453.
Jucá, M. J., Bandeira, B. C., Carvalho, D. S., & Leal, A. T. (2014). Estudo comparativo das substâncias 1,2-dimetil-hidrazina e azoximetano na indução de câncer colorretal em ratos. Journal of Coloproctology, 34(3), 167–173. https://doi.org/10.1016/j.jcol.2014.06.003
Doi, K., Fujioka, M., Sokuza, Y., Ohnishi, M., Gi, M., Takeshita, M., … Wanibuchi, H. (2017). Chemopreventive action by ethanol-extracted Brazilian green propolis on post-initiation phase of inflammation-associated rat colon tumorigenesis. In Vivo, 31(2), 187–197. https://doi.org/10.21873/invivo.11044
Chari, K. Y., Polu, P. R., & Shenoy, R. R. (2018). An appraisal of pumpkin seed extract in 1, 2-dimethylhydrazine induced colon cancer in Wistar rats. Journal of Toxicology, 1–12. https://doi.org/10.1155/2018/6086490
Bird, R. P. (1995). Role of aberrant crypt foci in understanding the pathogenesis of colon cancer. Cancer Letters, 93, 55–71.
David, S. R., Abd Malek, N., Mahadi, A. H., Chakravarthi, S., & Rajabalaya, R. (2018). Development of controlled release silicone adhesive–based mupirocin patch demonstrates antibacterial activity on live rat skin against Staphylococcus aureus. Drug Design, Development and Therapy, 12, 481–494. https://doi.org/10.2147/DDDT.S146549
Nair, A. B., & Jacob, S. (2016). A simple practice guide for dose conversion between animals and human. Journal of basic and clinical pharmacy, 7(2), 27–31. https://doi.org/10.4103/0976-0105.177703
Qiao, J., Gu, C., Shang, W., Du, J., Yin, W., Zhu, M., … Lu, W. (2011). Effect of green tea on pharmacokinetics of 5-fluorouracil in rats and pharmacodynamics in human cell lines in vitro. Food and Chemical Toxicology, 49(6), 1410–1415. https://doi.org/10.1016/j.fct.2011.03.033
Higdon, J. V., & Frei, B. (2003). Tea catechins and polyphenols: Health effects, metabolism, and antioxidant functions. Critical Reviews in Food Science and Nutrition, 43(1), 89–143. https://doi.org/10.1080/10408690390826464
De Robertis, M., Massi, E., Poeta, M. L., Carotti, S., Cecchetelli, L., Signori, E., & Fazio, V. M. (2011). The AOM/DSS murine model for the study of colon carcinogenesis: From pathways to diagnosis and therapy studies. Journal of Carcinogenesis, 12(22), 1–20. https://doi.org/10.4103/1477
Hanahan, D., & Weinberg, R. A. (2000). The hallmarks of cancer. Cell, 100, 57–70. https://doi.org/10.1007/BF03091804
Sadik, N. A. H. (2013). Chemopreventive efficacy of green tea drinking against 1,2-dimethyl hydrazine-induced rat colon carcinogenesis. Cell Biochemistry and Function, 31(3), 196–207. https://doi.org/10.1002/cbf.2873
Hayakawa, S., Saito, K., Miyoshi, N., Ohishi, T., Oishi, Y., Miyoshi, M., & Nakamura, Y. (2016). Anti-cancer effects of green tea by either anti- or pro-oxidative mechanisms. Asian Pacific Journal of Cancer Prevention, 17(4), 1649–1654. https://doi.org/10.7314/APJCP.2016.17.4.1649
Perše, M., & Cerar, A. (2011). Morphological and molecular alterations in 1,2 dimethylhydrazine and azoxymethane induced colon carcinogenesis in rats. Journal of Biomedicine and Biotechnology, 2011(May). https://doi.org/10.1155/2011/473964
Femia, A., & Caderni, G. (2008). Rodent models of colon carcinogenesis for the study of chemopreventive activity of natural products. Planta Medica, 74(13), 1602–1607. https://doi.org/10.1055/s-2008-1074577
Idris, A., Zulkipli, I. N., Zulhilmi, N. R., Lee, H. F., Rajabalaya, R., Lim, Y. C., … David, S. R. (2017). Melastoma malabathricum ethyl acetate fraction induces secondary necrosis in human breast and lung cancer cell lines. Pharmacognosy Magazine, 13, S688-92. https://doi.org/10.4103/pm.pm
Sipos, F., & Muzes, G. (2011). Isolated lymphoid follicles in colon: Switch points between inflammation and colorectal cancer? World Journal of Gastroenterology, 17(13), 1666–1673. https://doi.org/10.3748/wjg.v17.i13.1666
Musa, M. N., David, S. R., Zulkipli, I. N., Mahadi, A. H., Chakravarthi, S., & Rajabalaya, R. (2017). Development and evaluation of exemestane-loaded lyotropic liquid crystalline gel formulations. Inland Waters, 7(4). https://doi.org/10.15171/bi.2017.27
Sadighparvar, S., Darband, S. G., Yousefi, B., Kaviani, M., Ghaderi-Pakdel, F., Mihanfar, A., … Majidinia, M. (2020). Combination of quercetin and exercise training attenuates depression in rats with 1,2-dimethylhydrazine-induced colorectal cancer: Possible involvement of inflammation and BDNF signalling. Experimental physiology, 105(9), 1598–1609. https://doi.org/10.1113/EP088605
Okda, T. M., Abd-Elghaffar, S. K., Katary, M. A., & Abd-Alhaseeb, M. M. (2021). Chemopreventive and anticancer activities of indomethacin and vitamin D combination on colorectal cancer induced by 1,2-dimethylhydrazine in rats. Biomedical reports, 14(2), 27. https://doi.org/10.3892/br.2020.1403
Wang, Y., **, H.-Y., Fang, M.-Z., Wang, X.-F., Chen, H., Huang, S.-L., … Wang, S.-M. (2020). Epigallocatechin gallate inhibits dimethylhydrazine-induced colorectal cancer in rats. World journal of gastroenterology, 26(17), 2064–2081. https://doi.org/10.3748/wjg.v26.i17.2064
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Dr Sheba designed the experiments and organized the execution of the studies. Dr Rajan designed the experiments for the preparation of the extracts and the nanoparticle preparation. Ms. Khairunnasibah performed the experiments. The rest of the authors contributed equally to the studies.
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The research ethics for using animals were reviewed and approved by the University Research Ethics Committee (UREC), Universiti Brunei Darussalam (Ref: UBD/OAVCR/UREC/Dec18-02). Either gender of 2–3-month-old Wistar rats, which initially weighed 230–280 g, was procured from the animal house of the Institute of Health Science, Universiti Brunei Darussalam. Food and water were provided ad libitum and housed under standard conditions (27 ± 2 °C; 70–80% humidity; and 12 h light/12 h darkness cycle) with a minimum of 5 days for acclimatization to housing condition, prior to the intervention.
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David, S.R., Abdullah, K., Shanmugam, R. et al. Green Synthesis, Characterization and In Vivo Evaluation of White Tea Silver Nanoparticles with 5-Fluorouracil on Colorectal Cancer. BioNanoSci. 11, 1095–1107 (2021). https://doi.org/10.1007/s12668-021-00905-7
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DOI: https://doi.org/10.1007/s12668-021-00905-7