Illuminating new possibilities: Effects of copper oxide nanoparticles on gastrointestinal adenocarcinoma cells in hypoxic condition

Abstract

Cancer remains a major global health concern, necessitating the development of novel therapeutic approaches. Hypoxia is a common characteristic of solid tumors that plays a critical role in tumor progression, making it a prime target for anticancer therapies. This study aimed to determine the effects of copper oxide nanoparticles (CuONPs) on human gastrointestinal cancer cells in hypoxic condition for the first time. Toxicity of CuONPs was evaluated on human colon and gastric adenocarcinoma cells and normal fibroblasts by alamarBlue assay. Real-time polymerase chain reaction (PCR) was performed to study the effects of CuONPs on genes involved in cell apoptosis. To elucidate the molecular mechanisms underlying the effects of CuONPs in hypoxic condition, molecular docking was conducted on HIF-1α. Results revealed dose- and cell-type-dependent toxic effects of CuONPs, as a more significant (p < 0.0001) decrease in viability of LoVo cells (23 %) was observed compared to MKN-45 and HDF cells. In addition, CuONPs significantly (p < 0.0001) reduced LoVo cell viability down to 30.2 % in hypoxic condition. Gene expression analysis revealed significant (p < 0.0001) overexpression of P53 and BAX but downregulation of BCL-2 and CCND1 after treatment with CuONPs. Molecular docking indicated the preferable binding of CuONPs to the HIF-1α PAS-B domain through interaction with 15 residues with −4.8 kcal/mol binding energy. Our findings open up new possibilities for modulating HIF-1 activity and inhibiting hypoxia-induced tumor progression. Key summary: • CuONPs exhibited dose- and cell-type-dependent toxicity on colon and gastric adenocarcinoma cells and regulated the expression of apoptosis mediators. • Considerable effects of CuONPs on colon adenocarcinoma cells were retained in hypoxic condition. • Molecular docking revealed favorable interactions between CuONPs and residues within the HIF-1α PAS-B domain.

Keywords

• Hypoxia
• Copper oxide nanoparticles
• Anticancer properties
• Colon adenocarcinoma
• Gastric adenocarcinoma