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

Evyapan G., Ozdem B.

Bratislava Medical Journal, vol.127, no.1, pp.148-159, 2026 (SCI-Expanded, Scopus) identifier

  • Publication Type: Article / Article
  • Volume: 127 Issue: 1
  • Publication Date: 2026
  • Doi Number: 10.1007/s44411-025-00381-5
  • Journal Name: Bratislava Medical Journal
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, EMBASE
  • Page Numbers: pp.148-159
  • Keywords: Apoptosis, ATG5 siRNA, DNA damage, Gum Arabic, Ovarian neoplasms, Reactive oxygen species
  • Inonu University Affiliated: Yes

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 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.