Background: Quercetin is a flavonoid having anti-cancer properties; however, it has low stability, insufficient bioavailability, and poor solubility. This study aimed to load quercetin on nanoliposomes to enhance its efficiency against SW48 colorectal cancer cells. The cytotoxicity of free-quercetin and quercetin-loaded nanoliposomes on the expression of the epidermal growth factor receptor (EGER) gene was investigated. Methods: This present in vitro study was conducted at Yasuj University of Medical Sciences (Yasuj, Iran) in 2021. In this in vitro study, the lipid thin-film hydration method was used to synthesize quercetin-loaded liposomes. Additionally, high-performance liquid chromatography (HPLC) analyses, dynamic light scattering (DLS), and transmission electron microscopy (TEM) investigations were used to characterize nanomaterials. Following that, MTT, flow cytometry, and real-time PCR were used to investigate the cytotoxicity of quercetin-loaded liposomes on the colorectal cancer cells SW48 cell line, the incidence of apoptosis, and the expression of the EGFR gene in these cells. Statistical analysis was performed using the SPSS (version 26.0), and the graphs were created with the GraphPad Prism version 8.4.3. P<0.05 was considered statistically significant. Results: The nanoparticles were spherical, homogenous, and 150±10 nm in size. According to HPLC, Quercetin had a 98% loading capacity. Although both free quercetin and quercetin-loaded liposomes indicated significant cytotoxicity against cancer cells (P˂0.001), the combined form was significantly more active (P=0.008). 50 µg/mL of this compound reduced the viability of SW48 cells by more than 80% (IC50: 10.65 µg/mL), while the viability of cells treated with free quercetin was only 66% (IC50: 18.74 µg/mL). The apoptosis was nearly doubled in the cells treated with quercetin-loaded nanoliposomes compared to free quercetin (54.8% versus 27.6%). EGFR gene expression, on the other hand, was significantly lower in cells treated with quercetin-loaded liposomes than the quercetin alone (P=0.006). Conclusion: When combined with nanoliposomes, quercetin had greater anti-proliferative, apoptotic, and anti-EGFR expression than free quercetin. |
- Khazaei Z, Sohrabivafa M, Momenabadi V, Moayed L, Goodarzi E. Global cancer statistics 2018: Globocan estimates of incidence and mortality worldwide prostate cancers and their relationship with the human development index. Advances in Human Biology. 2019;9:245. doi: 10.4103/AIHB.AIHB_2_19.
- Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet. 2019;394:1467-80. doi: 10.1016/S0140-6736(19)32319-0. PubMed PMID: 31631858.
- Lichtenstern CR, Ngu RK, Shalapour S, Karin M. Immunotherapy, Inflammation and Colorectal Cancer. Cells. 2020;9. doi: 10.3390/cells9030618. PubMed PMID: 32143413; PubMed Central PMCID: PMCPMC7140520.
- Mitchell D, Puckett Y, Nguyen QN. Literature Review of Current Management of Colorectal Liver Metastasis. Cureus. 2019;11:e3940. doi: 10.7759/cureus.3940. PubMed PMID: 30937238; PubMed Central PMCID: PMCPMC6433446.
- Sigismund S, Avanzato D, Lanzetti L. Emerging functions of the EGFR in cancer. Mol Oncol. 2018;12:3-20. doi: 10.1002/1878-0261.12155. PubMed PMID: 29124875; PubMed Central PMCID: PMCPMC5748484.
- Turkes C, Arslan M, Demir Y, Cocaj L, Rifati Nixha A, Beydemir S. Synthesis, biological evaluation and in silico studies of novel N-substituted phthalazine sulfonamide compounds as potent carbonic anhydrase and acetylcholinesterase inhibitors. Bioorg Chem. 2019;89:103004. doi: 10.1016/j.bioorg.2019.103004. PubMed PMID: 31129502.
- Wee P, Wang Z. Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways. Cancers (Basel). 2017;9. doi: 10.3390/cancers9050052. PubMed PMID: 28513565; PubMed Central PMCID: PMCPMC5447962.
- Hugo de Almeida V, Guimaraes IDS, Almendra LR, Rondon AMR, Tilli TM, de Melo AC, et al. Positive crosstalk between EGFR and the TF-PAR2 pathway mediates resistance to cisplatin and poor survival in cervical cancer. Oncotarget. 2018;9:30594-609. doi: 10.18632/oncotarget.25748. PubMed PMID: 30093972; PubMed Central PMCID: PMCPMC6078136.
- Gonzalez-Conchas GA, Rodriguez-Romo L, Hernandez-Barajas D, Gonzalez-Guerrero JF, Rodriguez-Fernandez IA, Verdines-Perez A, et al. Epidermal growth factor receptor overexpression and outcomes in early breast cancer: A systematic review and a meta-analysis. Cancer Treat Rev. 2018;62:1-8. doi: 10.1016/j.ctrv.2017.10.008. PubMed PMID: 29126017.
- Li QH, Wang YZ, Tu J, Liu CW, Yuan YJ, Lin R, et al. Anti-EGFR therapy in metastatic colorectal cancer: mechanisms and potential regimens of drug resistance. Gastroenterol Rep (Oxf). 2020;8:179-91. doi: 10.1093/gastro/goaa026. PubMed PMID: 32665850; PubMed Central PMCID: PMCPMC7333932.
- Khorrami S, Zarepour A, Zarrabi A. Green synthesis of silver nanoparticles at low temperature in a fast pace with unique DPPH radical scavenging and selective cytotoxicity against MCF-7 and BT-20 tumor cell lines. Biotechnol Rep (Amst). 2019;24:e00393. doi: 10.1016/j.btre.2019.e00393. PubMed PMID: 31763203; PubMed Central PMCID: PMCPMC6864360.
- Ganjouzadeh F, Khorrami S, Gharbi S. Controlled cytotoxicity of Ag-GO nanocomposite biosynthesized using black peel pomegranate extract against MCF-7 cell line. Journal of Drug Delivery Science and Technology. 2022;71:103340. doi: 10.1016/j.jddst.2022.103340.
- Dias MC, Pinto D, Silva AMS. Plant Flavonoids: Chemical Characteristics and Biological Activity. Molecules. 2021;26. doi: 10.3390/molecules26175377. PubMed PMID: 34500810; PubMed Central PMCID: PMCPMC8434187.
- Chae HS, Xu R, Won JY, Chin YW, Yim H. Molecular Targets of Genistein and Its Related Flavonoids to Exert Anticancer Effects. Int J Mol Sci. 2019;20. doi: 10.3390/ijms20102420. PubMed PMID: 31100782; PubMed Central PMCID: PMCPMC6566427.
- Tang SM, Deng XT, Zhou J, Li QP, Ge XX, Miao L. Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects. Biomed Pharmacother. 2020;121:109604. doi: 10.1016/j.biopha.2019.109604. PubMed PMID: 31733570.
- Lopez-Campos F, Candini D, Carrasco E, Berenguer Frances MA. Nanoparticles applied to cancer immunoregulation. Rep Pract Oncol Radiother. 2019;24:47-55. doi: 10.1016/j.rpor.2018.10.001. PubMed PMID: 30425606; PubMed Central PMCID: PMCPMC6223232.
- Salehi Najafabadi P, Delaviz H, Asfaram A, Jafari Barmak M, Ghanbari A, Alipour M, et al. Evaluation of the Biodistribution of Arginine, glycine, aspartic acid peptide-modified Nanoliposomes Containing Curcumin in Rats. Iranian Journal of Biotechnology. 2022;20:79-88.
- Dayani MA. A review on application of nanoparticles for cancer therapy. Immunopathologia Persa. 2019. doi: 10.15171/ipp.2019.17.
- Zhou X, Liu HY, Zhao H, Wang T. RGD-modified nanoliposomes containing quercetin for lung cancer targeted treatment. Onco Targets Ther. 2018;11:5397-405. doi: 10.2147/OTT.S169555. PubMed PMID: 30214245; PubMed Central PMCID: PMCPMC6128275.
- Khorrami S, Zarrabi A, Khaleghi M, Danaei M, Mozafari MR. Selective cytotoxicity of green synthesized silver nanoparticles against the MCF-7 tumor cell line and their enhanced antioxidant and antimicrobial properties. Int J Nanomedicine. 2018;13:8013-24. doi: 10.2147/IJN.S189295. PubMed PMID: 30568442; PubMed Central PMCID: PMCPMC6267361.
- Jafari-Nasab T, Khaleghi M, Farsinejad A, Khorrami S. Probiotic potential and anticancer properties of Pediococcus sp. isolated from traditional dairy products. Biotechnol Rep (Amst). 2021;29:e00593. doi: 10.1016/j.btre.2021.e00593. PubMed PMID: 33598413; PubMed Central PMCID: PMCPMC7868823.
- Khaleghi M, Khorrami S. Down-regulation of biofilm-associated genes in mecA-positive methicillin-resistant S. aureus treated with M. communis extract and its antibacterial activity. AMB Express. 2021;11:85. doi: 10.1186/s13568-021-01247-z. PubMed PMID: 34110520; PubMed Central PMCID: PMCPMC8192652.
- Tajadini M, Panjehpour M, Javanmard SH. Comparison of SYBR Green and TaqMan methods in quantitative real-time polymerase chain reaction analysis of four adenosine receptor subtypes. Adv Biomed Res. 2014;3:85. doi: 10.4103/2277-9175.127998. PubMed PMID: 24761393; PubMed Central PMCID: PMCPMC3988599.
- Cheng CC, Lin HC, Tsai KJ, Chiang YW, Lim KH, Chen CG, et al. Epidermal growth factor induces STAT1 expression to exacerbate the IFNr-mediated PD-L1 axis in epidermal growth factor receptor-positive cancers. Mol Carcinog. 2018;57:1588-98. doi: 10.1002/mc.22881. PubMed PMID: 30035369.
- Reyes-Farias M, Carrasco-Pozo C. The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism. Int J Mol Sci. 2019;20. doi: 10.3390/ijms20133177. PubMed PMID: 31261749; PubMed Central PMCID: PMCPMC6651418.
- Li X, Zhou N, Wang J, Liu Z, Wang X, Zhang Q, et al. Quercetin suppresses breast cancer stem cells (CD44(+)/CD24(-)) by inhibiting the PI3K/Akt/mTOR-signaling pathway. Life Sci. 2018;196:56-62. doi: 10.1016/j.lfs.2018.01.014. PubMed PMID: 29355544.
- Baby B, Antony P, Vijayan R. Interactions of quercetin with receptor tyrosine kinases associated with human lung carcinoma. Nat Prod Res. 2018;32:2928-31. doi: 10.1080/14786419.2017.1385015. PubMed PMID: 29022361.
- Almasaudi SB. Acinetobacter spp. as nosocomial pathogens: Epidemiology and resistance features. Saudi J Biol Sci. 2018;25:586-96. doi: 10.1016/j.sjbs.2016.02.009. PubMed PMID: 29686523; PubMed Central PMCID: PMCPMC5910652.
- Thavarajah P, Sarker A, Materne M, Vandemark G, Shrestha R, Idrissi O, et al. A global survey of effects of genotype and environment on selenium concentration in lentils (Lens culinaris L.): Implications for nutritional fortification strategies. Food Chemistry. 2011;125:72-6. doi: 10.1016/j.foodchem.2010.08.038.
- Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4:807-18. doi: 10.1021/mp700113r. PubMed PMID: 17999464.
- Alam S, Mattern-Schain SI, Best MD. Targeting and Triggered Release Using Lipid-Based Supramolecular Assemblies as Medicinal Nanocarriers. In: Atwood JL, editor. Comprehensive Supramolecular Chemistry II. Oxford: Elsevier; 2017. p. 329-64.
- Imran M, Iqubal MK, Imtiyaz K, Saleem S, Mittal S, Rizvi MMA, et al. Topical nanostructured lipid carrier gel of quercetin and resveratrol: Formulation, optimization, in vitro and ex vivo study for the treatment of skin cancer. Int J Pharm. 2020;587:119705. doi: 10.1016/j.ijpharm.2020.119705. PubMed PMID: 32738456.
- Liu X, Zhang Y, Liu L, Pan Y, Hu Y, Yang P, et al. Protective and therapeutic effects of nanoliposomal quercetin on acute liver injury in rats. BMC Pharmacol Toxicol. 2020;21:11. doi: 10.1186/s40360-020-0388-5. PubMed PMID: 32059743; PubMed Central PMCID: PMCPMC7023747.
- Giordani B, Basnet P, Mishchenko E, Luppi B, Skalko-Basnet N. Utilizing Liposomal Quercetin and Gallic Acid in Localized Treatment of Vaginal Candida Infections. Pharmaceutics. 2019;12. doi: 10.3390/pharmaceutics12010009. PubMed PMID: 31861805; PubMed Central PMCID: PMCPMC7023398.
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