Unveiling the Distinct Effects of a Two-Dimensional Copper/Sodium Complex: Oxidative Stress on Erythrocytes and Cytotoxicity, Apoptosis, Drug Resistance, and Inflammation in Lung Cancer Cells.

Introduction: Copper complexes, as endogenous metals, have potential in cancer therapy, addressing issues associated with cisplatin. Since cisplatin uses Copper Transporter 1 (CTR1) for cellular entry, copper complexes may utilize this pathway to enhance transport efficiency.

Methods: The Cu/Na dipicolinic acid complex was synthesized to assess its cytotoxicity, induction of apoptosis, drug resistance, and inflammation in cancerous and normal lung cells. The effects of oxidative stress on erythrocytes were also examined.

Results: Cytotoxicity tests (MTT and SRB) showed superior inhibitory effects on A549 lung cancer cells compared to cisplatin, with no toxicity observed in MRC-5 normal lung fibroblast cells. Real-time PCR revealed increased caspase-3 expression (extrinsic apoptosis) for the complex compared to cisplatin, possibly due to CTR1- mediated entry. The complex did not induce drug resistance, as shown by AKT1 expression, and reduced TNF-α expression, preventing inflammation in normal cells. In contrast to cisplatin, the complex caused minimal oxidative stress in erythrocytes.

Discussion: It can be concluded that the Cu/Na dipicolinic acid complex may be easily transported by CTR1 to malignant tumors, particularly lung cancer. This complex has the ability to inhibit cancer cell growth and induce apoptosis in lung cancer cells. Therefore, copper complexes show promise as potential therapeutic options for treating this type of cancer.

Conclusion: The copper/sodium complex demonstrates enhanced therapeutic efficacy in lung cancer cells, requiring lower doses than cisplatin, while being safer for normal cells and erythrocytes.