3The 2D cell culture is the predominant in vitro model for numerous studies. 4 4 However, 2D cell cultures may not accurately reflect the functions of 4 5 three-dimensional (3D) tissues, which have extensive cell-cell and cell-matrix 4 6 interactions; thus, using 2D cell cultures may lead to inaccurate experimental results.
7Therefore, to obtain adequate and detailed information about the antioxidant activity 4 8 of cyanidin-3-O-glucoside (C3G) and C3G liposomes in the 2D and 3D cell culture 4 9 7 1 belongs to the flavonoid family and commonly present in human diet, exhibits 7 2 antiinflammatory and antioxidant effects 6-8 . Some studies have showed that C3G 7 3 protects from the adverse effects of radiation, controls the key aspects of 7 4 tumorigenesis, inhibits proliferation, induces apoptosis of cancer cells, reduces 7 5 oxidative stress, fights H 2 O 2 -induced oxidative stress in human embryonic kidney 7 6 cells, induces cell apoptosis and inhibit cell migration 9-15 . 7 7 Liposomes are vesicles, wherein the small aqueous volumes are surrounded by 7 8 bilayer membranes that are normally composed of phospholipids 16, 17 . Liposomes can 7 9 enhance the stability and bioavailability of encapsulated materials by protecting them 8 0 from external environment factors, making them ideal candidates for drug delivery 8 1 and important in food systemsy 18-21 . 8 2 The two-dimensional (2D) monolayer cell models have low anatomical and 8 3 physiological relevance and remain the predominant in vitro model for numerous 8 4 studies 22, 23 . However, some disadvantages exist in the use of the 2D monolayer cell 8 5 model in vitro in some studies. Growing concerns have been demonstrating that 8 6 monolayer and monotypic (2D) cellular screening assays may not effectively 8 7 reproduce the response of a three-dimensional (3D) solid tumor to pharmacological 8 8 compounds 24, 25 . In cancer research, the limitations of the 2D models are considered 8 9 one major reason for the approximately 95% of potential anticancer drugs failures in 9 0 clinical trials 26 . 9 1 The 3D spheroid cell culture systems are providing new insights into tumor 9 2 biology and also in differentiation, tissue organization, and homeostasis 27, 28 . Cells in 9 3 in vitro 3D culture systems are in league with their counterparts in vivo compared 9 4with cells grown as 2D monolayers, wherein 2D monolayer cells also exhibit altered 9 5 cell cycle durations, morphologies, susceptibility to drugs, metabolism, and gene and 9 6 protein expression levels 29, 30 . Cells cultured as 3D models exhibit features that are 9 7 close to the complex in vivo conditions 31 and have been proven realistic for 9 8 translating the study findings for in vivo applications; moreover, culturing cell lines as 9 93D models induces them to behave a step closer to the natural conditions 32, 33 . The 3D 3 1 9