Gum Arabic Modulates Redox–Ionic Microenvironments via Rheology and Kinetics to Induce Selective Cytotoxicity in Colorectal Cancer Cells
Cebeci E. Yüksel B. Aliusta R. Yılmaz Ş. Bursalıoğlu E.O. Bozyel M.E. Gökçe H.B. Kalay Ş. Kurtuluş Ş.Ö. Kurt A.A. Şahin F. Aslan I.
February 2026Multidisciplinary Digital Publishing Institute (MDPI)
Gels
2026#12Issue 2
Background: Gum Arabic (GA) is a natural polysaccharide widely recognized for its antioxidant and anti-inflammatory properties; however, its functional behavior as a biopolymeric gel and the mechanisms underlying its selective effects on cancer-related redox microenvironments remain insufficiently characterized. It is imperative to note that the interaction between its physicochemical properties and its biological activity in colorectal cancer remains to be fully clarified. Methods: This study aimed to evaluate the antineoplastic potential of GA in human colorectal cancer (CRC) cell lines (HT-29 and HCT-116) compared to normal fibroblasts (MRC-5) using the MTS assay. Oxidative stress-related molecular responses were assessed by quantitative PCR analysis of GPX4, GSTA2, CAT, NFKB, and SOD1 expression. In parallel, extracellular concentrations of key metal ions (Fe2+, Zn2+, Mn2+, Mg2+, Cu2+, and Al3+) were quantified following GA exposure. To establish its functional gel characteristics, rheological measurements were performed to assess viscosity and shear-dependent behavior, and USP-compliant in vitro kinetic studies were conducted to evaluate time-dependent release properties. Results: GA induced dose-dependent cytotoxicity in HT-29 and HCT-116 colorectal cancer cells, while MRC-5 fibroblasts exhibited comparatively higher viability across the tested concentration range, indicating reduced sensitivity in normal cells. Rheological analysis revealed concentration- and ion-dependent viscoelastic behavior, identifying a 10% (w/w) GA formulation as optimal due to its balanced low-shear viscosity and controlled shear-thinning properties. Kinetic studies demonstrated a defined, diffusion-governed release profile under physiologically relevant conditions. At the molecular level, significant upregulation of GPX4 and GSTA2 was observed in both cancer cell lines, whereas NFKB expression increased selectively in HT-29 cells, with no notable changes in CAT or SOD1 expression. Additionally, GA treatment resulted in marked increases in Fe2+, Zn2+, and Mn2+ levels, indicating modulation of the redox–ionic microenvironment. Conclusions: These findings demonstrate that GA functions as a natural, ion-responsive biopolymeric system with defined rheological and kinetic properties, capable of selectively targeting colorectal cancer cells through coordinated genetic and ionic regulation of oxidative stress. Collectively, the results position GA as a promising functional gel-based platform for future redox-modulated therapeutic strategies in colorectal cancer.
colorectal cancer , functional gels , Gum Arabic , kinetic behavior , redox modulation , rheology
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Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Kayışdağı, Istanbul, 34755, Turkey
Venar Sağlık A. S., Başkent Organized Industrial Zone, Teknokent Blvd. No:39, Malıköy, Sincan, Ankara, 06909, Turkey
Department of Medical Services and Techniques, Vocational School of Health Services, Sinop University, Sinop, 57000, Turkey
SFA R&D Private Health Services Co., Ltd, Teknopark Blv, No:1 3A Z01, Teknopark Istanbul, Pendik, Istanbul, 34890, Turkey
Department of Pharmaceutical Technology, Faculty of Pharmacy, Afyonkarahisar Health Sciences University, Afyonkarahisar, 03030, Turkey
Division of Biochemistry, Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, University of Health Sciences, Istanbul, 34668, Turkey
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, University of Health Sciences, Istanbul, 34668, Turkey
Department of Pharmaceutical Technology, Faculty of Pharmacy, Suleyman Demirel University, Türkiye, Isparta, 32000, Kazakhstan
Polisome R&D Pharmaceutical Industry Trade Company, Isparta, 32000, Turkey
ATABIO Technologies Co., Ltd., Teknopol İstanbul, Istanbul, 34903, Turkey
Department of Pharmaceutical Technology, Hamidiye Faculty of Pharmacy, University of Health Sciences, Istanbul, 34668, Turkey
Department of Genetics and Bioengineering
Venar Sağlık A. S.
Department of Medical Services and Techniques
SFA R&D Private Health Services Co.
Department of Pharmaceutical Technology
Division of Biochemistry
Department of Pharmaceutical Toxicology
Department of Pharmaceutical Technology
Polisome R&D Pharmaceutical Industry Trade Company
ATABIO Technologies Co.
Department of Pharmaceutical Technology
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