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

Abstract

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 mu M 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 similar 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. [GRAPHICS]