Nanosomal Docetaxel Promotes Ferroptosis-associated Biochemical Alteration in Michigan Cancer Foundation-7 Breast Cancer Cells
Vasudha Kamath, Sreedev Namboodiri, Sudharshan PrabhuBackground:
Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation and oxidative stress and emerging as a promising target for cancer therapy. Taxanes such as docetaxel (DTX) are widely used chemotherapeutics but require solvents such as polysorbate-80 and ethanol, which can cause hypersensitivity reactions. Nanosomal DTX lipid suspension (NDLS), a lipid-based formulation, improves drug stability, solubility, and permeability.
Methods:
Human breast cancer cells (Michigan Cancer Foundation [MCF]-7) were treated with increasing concentrations of NDLS (1–50 μM) for 48 h. Cell viability was determined by MTT assay to derive the half-maximal inhibitory concentration (IC
50
). Ferroptosis-associated parameters, including intracellular ferrous iron (Fe
2+
), reduced glutathione (GSH), and reactive oxygen species (ROS) levels, were quantified using standard biochemical assays. Cell death profiles were analyzed by flow cytometry using Annexin V-Fluorescein Isothiocyanate (FITC)/7-aminoactinomycin D (7-AAD) dual staining. All assays were conducted in biological triplicate (
Results:
NDLS treatment showed a concentration-dependent reduction in MCF-7 cell viability after 48 h with an IC 50 of 26 µM. NDLS exposure significantly increased intracellular Fe 2 ⁺ levels and ROS generation. Intracellular GSH levels showed a marked dose-dependent depletion compared with those of untreated controls. Flow cytometric analysis using Annexin V-FITC/7-AAD staining demonstrated a substantial reduction in viable cells with a concomitant increase in Annexin V-/7-AAD-positive populations.
Conclusions:
These findings suggest that NDLS induces oxidative and biochemical alterations associated with ferroptosis in MCF-7 breast cancer cells.