Anti-cancer effects of nanoemulsion prepared using Zingiber Officinale L. tincture against PC3 prostate cancer cells

Document Type : Research Paper

Authors

Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran

Abstract

Objective(s): The purpose of this work was to estimate the anti-cancer properties of the nanoemulsions synthesized by Zingiber officinale L. tincture against PC3 prostate cancer cells. 
Materials and Methods: Fresh ginger was initially procured from a local market, and extraction was performed after complete washing. In the next step, a nanoemulsion containing ginger extract was prepared using Tween 80, and its size and zeta potential were determined by a Zetasizer. The prepared nanoemulsion was assessed by transmission electron microscopy (TEM) to confirm the size and morphology of the particles. The toxicity of the nanoemulsion containing ginger extract against PC3 prostate cancer cells and normal HFF skin cells was evaluated using the MTT assay. To determine apoptosis, flow cytometry was used to assess cell cycle changes. In addition, the antioxidant activity of the nanoemulsion was estimated by DPPH and ABTS free radical scavenging tests. 
Results: The results showed that the prepared nanoparticles had a size of 67 nm (confirmed by TEM electron microscopy) and a zeta potential of -25.05 mV. The results of the MTT assay showed inverse dose-dependent toxicity for different concentrations of ginger nanoemulsion against PC3 cells. In addition to anti-cancer activity, the nanoemulsion showed a potent ability to scavenge DPPH and ABTS free radicals. 
Conclusion: Our results showed that the nanoemulsions containing ginger extract had toxicity against PC3 cancer cells but not normal cells, indicating their applicability as a suitable option for treating PC.

Keywords


1.    Yazdi MET, Darroudi M, Amiri MS, Hosseini HA, Nourbakhsh F, Mashreghi M, et al. Anticancer, antimicrobial, and dye degradation activity of biosynthesised silver nanoparticle using Artemisia kopetdaghensis. Micro Nano Lett. 2020;15(14):1046-1050.
2.    Mohammadzadeh V, Barani M, Amiri MS, Yazdi MET, Hassanisaadi M, Rahdar A, et al. Applications of plant-based nanoparticles in nanomedicine: A review. Sustain Chem Pharm. 2022;25:100606.
3.    Yazdi T, Ehsan M, Housaindokht MR, Sadeghnia HR, Esmaeilzadeh Bahabadi S, Amiri MS, et al. Assessment of phytochemical components and anti-oxidant activity of Rheum turkestanicum Janisch. Stud Med Sci. 2020;31(2):75-81.
4.    Zarei M, Karimi E, Oskoueian E, Es-Haghi A, Yazdi MET. Comparative study on the biological effects of sodium citrate-based and apigenin-based synthesized silver nanoparticles. Nutr Cancer 2021;73(8):1511-1519.
5.    Yazdi MET, Nourbakhsh F, Mashreghi M, Mousavi SH. Ultrasound-based synthesis of ZnO· Ag2O3 nanocomposite: characterization and evaluation of its antimicrobial and anticancer properties. Res Chem Intermed. 2021;47(3):1285-1296.
6.    Arazmjoo S, Es-haghi A, Mahmoodzadeh H. Evaluation of anti-cancer and anti-oxidant properties of nanoemulsions synthesized by Nigella Sativa L. tincture. Nanomed J. 2021;8(1).
7.    Klaunig JE, Wang Z, Pu X, Zhou S. Oxidative stress and oxidative damage in chemical carcinogenesis. Toxicol Appl Pharmacol. 2011;254(2):86-99.
8.    Es-haghi A, Javadi F, Yazdi MET, Amiri MS. The Expression of anti-oxidant Genes and Cytotoxicity of Biosynthesized Cerium Oxide Nanoparticles Against Hepatic Carcinoma Cell Line. Avicenna J Med Biochem. 2019;7(1):16-20.
9.    Matés JM, Pérez-Gómez C, De Castro IN. Anti-oxidant enzymes and human diseases. Clin Biochem. 1999;32(8):595-603.
10.    Rezaei MR, Es-haghi A, Yaghmaei P, Ghobeh M. Biological fabrication of Ag/Ag2O nanoparticles by Haplophyllum obtusifolium watery extract: characterisation and estimation of its biochemical activities. Micro Nano Lett. 2020; 15(13):898-902.
11.    Hatami A, Heydarinasab A, Akbarzadehkhiyavi A, Pajoum Shariati F. An Introduction to Nanotechnology and Drug Delivery. Chem Methodol. 2021;5(2):153-165.
12.    Javad Farhangi M, Es-haghi A, Taghavizadeh Yazdi ME, Rahdar A, Baino F. MOF-Mediated Synthesis of CuO/CeO2 Composite Nanoparticles: Characterization and Estimation of the Cellular Toxicity against Breast Cancer Cell Line (MCF-7). J Funct Biomater. 2021;12(4):53.
13.    Javadi F, Yazdi MET, Baghani M, Es-haghi A. Biosynthesis, characterization of cerium oxide nanoparticles using Ceratonia siliqua and evaluation of anti-oxidant and cytotoxicity activities. Mater Res Express. 2019;6(6):065408.
14.    Shamasi Z, Es-haghi A, Taghavizadeh Yazdi ME, Amiri MS, Homayouni-Tabrizi M. Role of Rubia tinctorum in the synthesis of zinc oxide nanoparticles and apoptosis induction in breast cancer cell line. Nanomed J. 2021; 8(1): 65-72.
15.    Es-haghi A, Taghavizadeh Yazdi ME, Sharifalhoseini M, Baghani M, Yousefi E, Rahdar A, et al. Application of Response Surface Methodology for Optimizing the Therapeutic Activity of ZnO Nanoparticles Biosynthesized from Aspergillus niger. Biomimetics. 2021;6(2):34.
16.    Mousavi-Kouhi SM, Beyk-Khormizi A, Amiri MS, Mashreghi M, Yazdi ME. Silver-zinc oxide nanocomposite: From synthesis to antimicrobial and anticancer properties. Ceramics International. 2021;47(15):21490-21497.
17.    Taghavizadeh Yazdi M, Darroudi, M, Amiri, MS, Zarrinfar, H, Hosseinie HA, Mashreghi M, Mozafarri H, Ghorbani A, Mousavi SH. Antimycobacterial, anticancer, anti-oxidant, and photocatalytic activity of biosynthesized silver nanoparticles using Berberis integerrima Iranian. Iran J Sci Technol Trans A 2021;46(1):1-11.
18.    Ashna M, Es-Haghi A, Karimi Noghondar M, Al Amara D, Yazdi ME. Greener synthesis of cerium oxide nanoemulsion using pollen grains of Brassica napus and evaluation of its antitumour and cytotoxicity properties. Materials Technology. 2020;31:1-8.
19.    Shakerimanesh K, Bayat F, Shahrokhi A, Baradaran A, Yousefi E, Mashreghi M, et al. Biomimetic synthesis and characterisation of homogenouse gold nanoparticles and estimation of its cytotoxity against breast cancer cell line. Mater Techno. 2022:1-8.
20.    Ashna M, Es-Haghi A, Karimi Noghondar M, Al Amara D, Yazdi MET. Greener synthesis of cerium oxide nanoemulsion using pollen grains of Brassica napus and evaluation of its antitumour and cytotoxicity properties. Mater Technol. 2020:1-8.
21.    Yukuyama M, Ghisleni D, Pinto T, Bou‐Chacra N. Nanoemulsion: process selection and application in cosmetics–a review. Int J Cosmet Sci. 2016;38[1):13-24.
22.    Mahmood S. A critical review on pharmaceutical and medicinal importance of ginger. Act Sci Nutr Health. 2019;3:78-82.
23.    Grzanna R, Lindmark L, Frondoza CG. Ginger—an herbal medicinal product with broad anti-inflammatory actions. J Med Food. 2005;8(2):125-132.
24.    Amiri MS, Joharchi MR, TaghavizadehYazdi ME. Ethno-medicinal plants used to cure jaundice by traditional healers of Mashhad, Iran. Iran J Pharm Res. 2014;13[1):157.
25.    Amiri MS, Yazdi MET, Rahnama M. Medicinal plants and phytotherapy in Iran: Glorious history, current status and future prospects. Plant Sci Today. 8(1):95-111.
26.    Afzal Μ, Al-Hadidi D, Menon M, Pesek J, Dhami M. Ginger: an ethnomedical, chemical and pharmacological review. Drug Metab Pharmacokinet. 2001;18(3-4):159-190.
27.    Bhowmik D, Tripathi K, Chandira M, Kumar K. Zingiber officinale the herbal and traditional medicine and its therapeutically importance. RJPP. 2010;2(2):102-110.
28.    Nair KP. Ginger as a Spice and Flavorant. Turmeric (Curcuma longa L) and Ginger (Zingiber officinale Rosc)-World’s Invaluable Medicinal Spices: Springer; 2019. p. 541-54.
29.    Shukla Y, Singh M. Cancer preventive properties of ginger: a brief review. Food Chem Toxicol 2007;45(5):683-690.
30.    Abdullah S, Abidin SAZ, Murad NA, Makpol S, Ngah WZW, Yusof YAM. Ginger extract (Zingiber officinale) triggers apoptosis and G0/G1 cells arrest in HCT 116 and HT 29 colon cancer cell lines. Afr J Biochem Res. 2010;4(5):134-142.
31.    Ugwoke CE, Nzekwe U. Phytochemistry and proximate composition of ginger (Zingiber officinale). Journal of Pharmaceutical and Allied Sciences. 2010;7(5):1182-1187.
32.    Gunathilake K, Rupasinghe HV. Recent perspectives on the medicinal potential of ginger. Botanics: Targets and Therapy. 2015;5:55-63.
33.    Zick SM, Djuric Z, Ruffin MT, Litzinger AJ, Normolle DP, Alrawi S, et al. Pharmacokinetics of 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol and conjugate metabolites in healthy human subjects. Cancer Epidemiol. Biomarkers Prev. 2008;17(8):1930-1936.
34.    Dunn MW, Kazer MW, editors. Prostate cancer overview. Seminars in oncology nursing; 2011: Elsevier.
35.    Taneja P, Sharma S, Sinha VB, Yadav AK. Advancement of nanoscience in development of conjugated drugs for enhanced disease prevention. Life Sci. 2021;268:118859.
36.    Ahmad M, Sahabjada JA, Hussain A, Badaruddeen MA, Mishra A. Development of a new rutin nanoemulsion and its application on prostate carcinoma PC3 cell line. Excli Journal. 2017;16:810.
37.    Asgari HT, Es-haghi A, Karimi E. Anti-angiogenic, antibacterial, and anti-oxidant activities of nanoemulsions synthesized by Cuminum cyminum L. tinctures. J. Food Meas. Charact. 2021:1-11.
38.    Taghavizadeh Yazdi ME, Hamidi A, Amiri MS, Kazemi Oskuee R, Hosseini HA, Hashemzadeh A, et al. Eco-friendly and plant-based synthesis of silver nanoparticles using Allium giganteum and investigation of its bactericidal, cytotoxicity, and photocatalytic effects. Mater Technol. 2019;34(8):490-497.
39.    Yazdi MET, Modarres M, Amiri MS, Darroudi M. Phyto-synthesis of silver nanoparticles using aerial extract of Salvia leriifolia Benth and evaluation of their antibacterial and photo-catalytic properties. Res Chem Intermed. 2019;45(3):1105-1116.
40.    Klang V, Matsko NB, Valenta C, Hofer F. Electron microscopy of nanoemulsions: an essential tool for characterisation and stability assessment. Micron. 2012;43(2-3):85-103.
41.    Hamidi A, Yazdi MET, Amiri MS, Hosseini HA, Darroudi M. Biological synthesis of silver nanoparticles in Tribulus terrestris L. extract and evaluation of their photocatalyst, antibacterial, and cytotoxicity effects. Res Chem Intermed. 2019;45(5):2915-2925.
42.    Yazdi MET, Amiri MS, Hosseini HA, Oskuee RK, Mosawee H, Pakravanan K, et al. Plant-based synthesis of silver nanoparticles in Handelia trichophylla and their biological activities. Bull Mater Sci. 2019;42(4):155.
43.    Tolosa L, Donato MT, Gómez-Lechón MJ. General cytotoxicity assessment by means of the MTT assay.  Protocols in in vitro hepatocyte research: Springer; 2015. p. 333-348.
44.    Darzynkiewicz Z, Bedner E, Smolewski P, editors. Flow cytometry in analysis of cell cycle and apoptosis. Seminars in hematology; 2001: Elsevier.
44.    Yazdi MET, Khara J, Husaindokht MR, Reza H, Sadeghnia SEB, Amiri MS, et al. Biocomponents and anti-oxidant activity of Ribes khorasanicum. IJBSM. 2018;3(3):99-103.
45.    Ozgen M, Reese RN, Tulio AZ, Scheerens JC, Miller AR. Modified 2, 2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) method to measure anti-oxidant capacity of selected small fruits and comparison to ferric reducing anti-oxidant power (FRAP) and 2, 2 ‘-diphenyl-1-picrylhydrazyl (DPPH) methods. J Agric Food Chem. 2006;54(4):1151-1157.
46.    Amiri MS, Mohammadzadeh V, Yazdi MET, Barani M, Rahdar A, Kyzas GZ. Plant-Based Gums and Mucilages Applications in Pharmacology and Nanomedicine: A Review. Molecules. 2021;26(6):1770.
47.    Mobaraki F, Momeni M, Yazdi MET, Meshkat Z, Toosi MS, Hosseini SM. Plant-derived synthesis and characterization of gold nanoparticles: Investigation of its anti-oxidant and anticancer activity against human testicular embryonic carcinoma stem cells. Process Biochem 2021.
48.    Hashemzadeh MR, Yazdi MET, Amiri MS, Mousavi SH. Stem Cell Therapy in the Heart: Biomaterials as A Key Route. Tissue Cell. 2021:101504.
49.    Modarres M, Yazdi MET. Elicitation Improves Phenolic Acid Content and anti-oxidant Enzymes Activity in Salvia leriifolia Cell Cultures. Iran J Sci Technol Trans A Sci.  2021:1-7.
50.    Darroudi M, Yazdi MET, Amiri MS. Plant-Mediated Biosynthesis of Nanoparticles. 21st Century Nanoscience–A Handbook: CRC Press; 2020. p. 1-18.
51.    Farsi M, Taghavizadeh YM, Qasemiomran V. Micropropagation of Anthurium andreanum cv. Terra. Afr J Biotechnol. 2012;11(68):13162-13166.
52.    Modarres M, Bahabadi SE, Yazdi MET. Enhanced production of phenolic acids in cell suspension culture of Salvia leriifolia Benth. using growth regulators and sucrose. Cytotechnology. 2018:1-10.
53.    Yazdi MET, Amiri MS, Akbari S, Sharifalhoseini M, Nourbakhsh F, Mashreghi M, et al. Green Synthesis of Silver Nanoparticles Using Helichrysum graveolens for Biomedical Applications and Wastewater Treatment. Bionanoscience. 2020:1-7.
54.    Eddouks M, Chattopadhyay D, De Feo V, Cho WC. Medicinal plants in the prevention and treatment of chronic diseases. Hindawi; 2012.
55.    Yazdi MET, Khara J, Sadeghnia HR, Bahabadi SE, Darroudi M. Biosynthesis, characterization, and antibacterial activity of silver nanoparticles using Rheum turkestanicum shoots extract. Res Chem Intermed. 2018;44(2):1325-34.
56. Petrovska BB. Historical review of medicinal plants’ usage. Pharmacognosy reviews. 2012;6(11):1. 1-5.
57.    Jabir NR, Tabrez S, Ashraf GM, Shakil S, Damanhouri GA, Kamal MA. Nanotechnology-based approaches in anticancer research. Int J Nanomedicine. 2012;7:4391–4408.
58.    Gordaliza M. Natural products as leads to anticancer drugs. Clin Transl Oncol  2007;9(12):767-776.
59.    Mattheolabakis G, Rigas B, Constantinides PP. Nanodelivery strategies in cancer chemotherapy: biological rationale and pharmaceutical perspectives. Nanomedicine. 2012;7(10):1577-1590.
60.    Dai Y, Xu C, Sun X, Chen X. Nanoparticle design strategies for enhanced anticancer therapy by exploiting the tumour microenvironment. Chem Soc Rev. 2017;46(12):3830-5382.
61.    Zhang J, Li X, Huang L. Anticancer activities of phytoconstituents and their liposomal targeting strategies against tumor cells and the microenvironment. Adv Drug Deliv Rev. 2020;154:245-273.
62.    Ansari JA, Ahmad MK, Khan AR, Fatima N, Khan HJ, Rastogi N, et al. Anticancer and anti-oxidant activity of Zingiber officinale Roscoe rhizome. 2016;54(11):767-773.
63.    Wang W, Zhang L, Li N, Zu Y. Chemical composition and in vitro anti-oxidant, cytotoxicity activities of Zingiber officinale Roscoe essential oil. Afr J Biochem Res. 2012;6(6):75-80.
64.    Anggasta GG. Mikroenkapsulasi oleoresin jahe merah (zingiber officinale roxb. var. rubrum theilade) dengan pemanfaatan mucilage okra (abelmoschus esculentus l.)= Microencapsulation of red ginger root (zingiber officinale roxb. var. rubrum theilade) oleoresin by the utilization of okra (abelmoschus esculentus l.) mucilage: Universitas Pelita Harapan; 2015.
65.    Mulia K, Zaenal MF, Krisanti EA, Editors. Encapsulation of oleoresin from ginger (Zingiber officinale var. Roscoe) in vegetable oils based nanoemulsions: Preparation and characterization for oral delivery formulation. AIP Conference Proceedings; 2019: AIP Publishing LLC.
66.    Choudhury D, Das A, Bhattacharya A, Chakrabarti G. Aqueous extract of ginger shows antiproliferative activity through disruption of microtubule network of cancer cells. Food Chem Toxicol.  2010;48(10):2872-2880.
67.    Kent LN, Leone G. The broken cycle: E2F dysfunction in cancer. Nat Rev Cancer. 2019;19(6):326-338.