Abstract
Background: Gastric cancer, often linked to chronic Helicobacter pylori (H. pylori) infection, poses treatment challenges due to the bacterium's role in creating a pro-inflammatory microenvironment conducive to tumor development. Chronic infection induces oxidative stress, inflammatory cytokines, and genetic instability, contributing to cancer progression.
Aim: This study explores the antibacterial and anticancer synergy of Curcuma longa (turmeric) extract-loaded chitosan nanoparticles (CL-CSNPs) for combating H. pylori-associated gastric cancer.
Methods: CL-CSNPs were prepared using ionic gelation and characterized for particle size, surface charge, morphology, encapsulation efficiency, and in vitro drug release. Antibacterial activity against H. pylori was evaluated using minimum inhibitory concentration (MIC) and agar well diffusion (zone of inhibition) assays. Anticancer effects were assessed in AGS gastric cancer cells via MTT assay for cell viability, flow cytometry for apoptosis (Annexin V/PI), ROS quantification, caspase-3 enzyme-linked immunosorbent assay (ELISA), and pro-/anti-inflammatory cytokine profiling through multiplex assays.
Results: CL-CSNPs exhibited a particle size of 148.3 ± 2.1 nm, zeta potential of +30.6 ± 1.8 mV, and encapsulation efficiency of 80.2 ± 3.4%. MIC against H. pylori was 25 µg/mL with a 22.4 ± 1.5 mm zone of inhibition. CL-CSNPs reduced AGS cell viability by 70% at 100 µg/mL, significantly increased apoptosis, caspase-3 activity (50 ± 4 pg/mL), and ROS generation. They also downregulated IL-6 and IL-8 by over 60% and upregulated IL-10 expression, indicating anti-inflammatory and anticancer effects.
Conclusion: Our study shows that CL-CSNPs have shown impressive antibacterial properties against H. pylori, effectively slowing down bacterial growth and disrupting its role in causing gastric inflammation. In addition, this formulation has powerful effects on AGS gastric cancer cells, promoting cell death through increased production of reactive oxygen species and activation of caspase-3. Moreover, CL-CSNPs help regulate inflammatory responses by lowering levels of pro-inflammatory cytokines like IL-6 and IL-8 while boosting anti-inflammatory markers such as IL-10. This dual action helps reduce the tumor-promoting environment associated with inflammation. Overall, the results indicate that CL-CSNPs may serve as a promising treatment option, targeting both H. pylori infections and the progression of gastric cancer, thus offering an integrated approach for gastro-oncology therapies.

Key words: Curcuma longa, chitosan nanoparticles, Helicobacter pylori, gastric cancer, apoptosis, caspase-3.