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<p>Gum Arabic (GA) is a clinically safe plant-derived polysaccharide with potential anti-cancer activity. We evaluated the effects of GA alone and in combination with ATG5 siRNA-mediated inhibition of autophagy in chemoresistant A2780-ADR ovarian cancer cells. GA at a concentration of 30.68&#xa0;µM reduced cell viability to 47 ± 3% at 72&#xa0;h and increased intracellular ROS 2.3-fold (n = 3, p &lt; 0.001). The GA + ATG5 siRNA combination further decreased viability to ~ 30% and markedly enhanced apoptosis (Annexin V/PI, p &lt; 0.001). Western blot analysis revealed increased p53 protein levels and decreased Bcl-2 protein levels, as well as altered P-Chk1 protein levels, which are consistent with apoptosis associated with DNA damage. GA also caused a loss of mitochondrial membrane potential and treatment-dependent changes in UCP4/5 expression, indicating mitochondrial stress. These findings identify GA, particularly in combination with autophagy inhibition, as a low-toxicity agent with significant anti-proliferative effects in vitro. The study is limited to cell models; in-vivo validation and pharmacokinetic/delivery studies are required before clinical translation.</p> Graphical Abstract <p></p>

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Inhibition of Autophagy by ATG5 siRNA Transfection Enhances Anti-cancer Effects of Gum Arabic, Promotes Oxidative Stress-Mediated Apoptosis and Affects DNA Damage and Mitochondrial Membrane Potential in Ovarian Cancer Cells

  • 期刊论文

  • 发表日期：

    2025年10月17日

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  • Gulsah Evyapan,
  • Berna Ozdem

摘要

Gum Arabic (GA) is a clinically safe plant-derived polysaccharide with potential anti-cancer activity. We evaluated the effects of GA alone and in combination with ATG5 siRNA-mediated inhibition of autophagy in chemoresistant A2780-ADR ovarian cancer cells. GA at a concentration of 30.68 µM reduced cell viability to 47 ± 3% at 72 h and increased intracellular ROS 2.3-fold (n = 3, p < 0.001). The GA + ATG5 siRNA combination further decreased viability to ~ 30% and markedly enhanced apoptosis (Annexin V/PI, p < 0.001). Western blot analysis revealed increased p53 protein levels and decreased Bcl-2 protein levels, as well as altered P-Chk1 protein levels, which are consistent with apoptosis associated with DNA damage. GA also caused a loss of mitochondrial membrane potential and treatment-dependent changes in UCP4/5 expression, indicating mitochondrial stress. These findings identify GA, particularly in combination with autophagy inhibition, as a low-toxicity agent with significant anti-proliferative effects in vitro. The study is limited to cell models; in-vivo validation and pharmacokinetic/delivery studies are required before clinical translation.

Graphical Abstract