Copper oxide nanoparticles function as antineoplastic agents in uterine cancer cell lines

Abstract

Cancer of the uterine corpus is the fourth leading cancer and the fifth leading cause of cancer-related death in women in the United States. Chemotherapeutic resistance, specifically platinum-resistance, contributes to this problem. Therefore, an alternative treatment regimen is required. Using inorganic copper oxide nanoparticles (CuO NPs), we evaluated cancer cell responses indicative of anti-neoplastic activity. CuO NPs were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), dynamic light scattering (DLS) and laser Doppler velocimetry (LDV). The nanoparticles were rod-like and had a diameter of 70 {+/-} 30 nm and a copper content ranging from 77% - 82.6%. The hydrodynamic diameter and the zeta potential significantly decreased with more particles in solution. These materials were also used in four endometrial cancer cell lines and one cervical cancer cell line to evaluate cell viability, apoptosis, migration, and reactive oxygen species. In endometrial cancer cell lines, the IC50 values ranged from 1.028 ug/mL in HEC-1A cells to 73.62 ug/mL in Ishikawa cells, indicating that different cells have vastly different responses to CuO NPs. The results also indicated cell line-dependent differences in apoptosis, oxidation potential, and migration. Further, the cervical cancer cell line was modified using CRISPR technology to highlight a common germline mutation that causes earlier onset and more aggressive cancer progression. These genetic mutations resulted in differences in a loss of redox potential without observable changes in apoptosis or migration. The results of these studies indicate that CuO NPs elicit effects dependent upon the stage of cancer. Anticipated long-term applications of these studies includes the potential as a target-specific anti-cancer agent, designed using knowledge at the interface of colloids and the tumor environment. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/729888v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1e0fe68org.highwire.dtl.DTLVardef@5e776dorg.highwire.dtl.DTLVardef@1f2aad6org.highwire.dtl.DTLVardef@add7fc_HPS_FORMAT_FIGEXP M_FIG C_FIG Copper oxide nanoparticles (CuO NPs) were characterized upon receipt using electron microscopy, elemental analysis, dynamic light scattering, laser Doppler velocimetry, and Fourier-transform infrared spectroscopy. These CuO NPs were exposed to HeLa cells with and without DNA mismatch repair deficiencies to assess the impacts on cancer cell migration, apoptosis, and redox potential.