Comparing the toxicity effects of copper oxide nanoparticles conjugated with Lapatinib on breast (MDA-MB-231) and lung (A549) cancer cell lines

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2024-09, Vol.397 (9), p.6855-6866
• Main Authors: Talarposhti, Masoumeh Valizadeh, Salehzadeh, Ali, Jalali, Amir
• Format: Article
• Language: English
• Subjects: A549 Cells; Antineoplastic Agents - pharmacology; Antineoplastic Agents - toxicity; Apoptosis; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell cycle; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cell size; Cell Survival - drug effects; Chromatin; Copper; Copper - toxicity; Female; Flow cytometry; Humans; Lapatinib - pharmacology; Light scattering; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Metal Nanoparticles - toxicity; Morbidity; Nanoparticles; Neurosciences; Pharmacology/Toxicology; Physicochemical properties; Reactive oxygen species; Reactive Oxygen Species - metabolism; S phase; Spectrum analysis; Toxicity; Transmission electron microscopy; Tumor cell lines; X-ray diffraction; X-ray spectroscopy; Zeta potential
• ISSN: 0028-1298; 1432-1912; 1432-1912
• DOI: 10.1007/s00210-024-03071-1

In recent years, the increase in cancer morbidity and mortality has presented scientists with a major challenge in developing new therapeutic agents against cancer cells. This study aims to characterize the anticancer effects of copper oxide nanoparticles (NPs) conjugated with Lapatinib (CuO@Lapatinib) on breast and lung cancer cell lines. The physicochemical properties of the NPs were characterized by fourier-transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), scanning and transmission electron microscopy, energy dispersive X-ray spectroscopy (EDS), dynamic light scattering (DLS), and zeta potential analyses. The antiproliferative potential of the NPs in the breast (MDA-MB-231) and lung (A549) cancer cell lines and a normal cell line (MRC5) was investigated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Flow cytometry and Hoechst staining were used to evaluate cell apoptosis and cell cycle analysis. The reactive oxygen species (ROS) levels in the treated and control cells were also determined. The NPs were spherical, with a size range of 20-59nm, a DLS size of 338nm, and a zeta potential of -42.9 mV. The half maximal inhibitory concentration (IC 50 ) of CuO@Lapatinib NPs for the normal, breast cancer, and lung cancer cell lines was 105, 98, and 87 µg/ml, respectively. Treatment with CuO@Lapatinib NPs caused considerable apoptosis induction in breast cancer (from 0.65% to 68.96%) and lung cancer cell lines (from 1.11% to 44.11%). Also, an increased level of cell cycle arrest at the S phase was observed in both cancer cell lines. The ROS level in the breast and lung cancer cell lines after treatment with CuO@Lapatinib NPs increased by 3.45 and 21.04 folds, respectively. Nuclear morphological alterations, including chromatin condensation and fragmentation, were observed in both cancer cell lines. This study indicates CuO@Lapatinib is a potent antiproliferative compound with more efficient inhibitory effects on lung cancer than breast cancer cells, which can be related to the higher ROS generation in the A549 cell line.