Yttrium Oxide nanoparticles induce cytotoxicity, genotoxicity, apoptosis, and ferroptosis in the human triple-negative breast cancer MDA-MB-231 cells.

BACKGROUND: Triple-negative breast cancer (TNBC) is a lethal mammary carcinoma subtype that affects females and is associated with a worse prognosis. Chemotherapy is the only conventional therapy available for patients with TNBC due to the lack of therapeutic targets. Yttrium oxide (Y2O3) is a rare earth metal oxide, whose nanoparticle (NPs) formulations are used in various applications, including biological imaging, the material sciences, and the chemical synthesis of inorganic chemicals. However, the biological activity of Y2O3-NPs against TNBC cells has not been fully explored. The current study was conducted to assess Y2O3-NPs' anticancer activity against the human TNBC MDA-MB-231 cell line. METHODS: Transmission electron microscopy (TEM), X-ray diffraction, Zeta potential, and dynamic light scattering (DLS) were used to characterize the Y2O3-NPs. SRB cell viability, reactive oxygen species (ROS) measurement, single-cell gel electrophoresis (comet assay), qPCR, flow cytometry, and Western blot were employed to assess the anticancer activity of the Y2O3-NPs. RESULTS: Our results indicate favorable physiochemical properties of Y2O3-NPs (with approximately average size 14 nm, Zeta Potential about - 53.2 mV, and polydispersity index = 0.630). Y2O3-NPs showed a potent cytotoxic effect against MDA-MB-231 cells, with IC50 values of 74.4 µg/mL, without cytotoxic effect on the normal retina REP1 and human dermal fibroblast HDF cell lines. Further, treatment of MDA-MB-231 cells with IC50 Y2O3-NPs resulted in increased oxidative stress, accumulation of intracellular ROS levels, and induced DNA damage assessed by Comet assay. Upon Y2O3-NPs treatment, a significant increase in the early and late phases of apoptosis was revealed in MDA-MB-231 cells. qPCR results showed that Y2O3-NPs significantly upregulated the pro-apoptotic genes CASP3 and CASP8 as well as ferroptosis-related gene heme oxygenase-1 (HO-1), whereas the anti-apoptotic gene BCL2 was significantly downregulated. CONCLUSION: This study suggests that Y2O3-NPs are safe on normal REP1 and HDF cells and exhibited a potent selective cytotoxic effect against the TNBC MDA-MB-231 cells through increasing levels of ROS generation with subsequent DNA damage, and induction of apoptosis and ferroptosis.

Growth retardation and apoptotic death of tumor cells by Artemisia herba-alba oral administration in Ehrlich solid carcinoma bearing mice

ABSTRACT At present, there is a rapidly growing interest in studying the cytotoxic effects of Artemisia herba alba Asso, Asteraceae, in various cancer cell lines. However, its antitumor effectiveness has not been investigated. Therefore, the current study was conducted to study the effect of A. herba alba extract on the proliferation and growth of solid tumor cells in Ehrlich Solid Carcinoma bearing mice. Oral administration of A. herba alba extract resulted in significant reductions in tumor size, tumor weight and mice body weight, as well as caused concurrent significant increases in the DNA breakages and apoptotic DNA damage induction in a time-dependent manner. A. herba alba extract also raised the expression level of p53 gene and reduced of K-ras expression in a time-dependent manner. Minor histological lesions were observed in the liver and kidney tissues sections of mice administered A. herba alba extract compared with the high histological lesions observed in the liver and kidney tissues of artesunate and cisplatin treated groups. Thus, we concluded that A. herba alba extract exhibited promising potential antitumor efficacy with greater safety than artesunate and the commercially used anticancer drug cisplatin in mice.