Integrated Transcriptomic and Biochemical Analyses Reveal Coordinated Suppression of ER-Associated Survival Signaling and Activation of ROS-Mediated Stress Responses by Oxidized Graphene Quantum Dots in Estrogen Receptor-Positive Breast Cancer

Oxidized graphene quantum dots (o-GQDs) alter viability and cell-cycle progression in breast cancer cells, yet the cellular programs underlying these effects remain incompletely defined. We exposed MCF-7 cells to 10 mg/L o-GQD for 72 h and integrated RNA sequencing with quantitative protein-marker, ROS, antioxidant-intervention, proteasome-inhibition, and puromycin-labeling analyses from independent experiments. Transcriptomic analyses showed significant negative enrichment of proliferative and cell-cycle programs (E2F Targets, G2M Checkpoint, MYC Targets V1), with complementary KEGG/Reactome evidence of attenuated estrogen-associated programs. Quantitative Western blotting showed dose-dependent reductions in ERα (to 41.36 ± 13.73% at 10 mg/L), p-RB (to 8.31 ± 10.39%), and Survivin (to 23.97 ± 19.01%), with p-ERK/ERK attenuation and marked γ-H2AX accumulation (345.21 ± 161.39%). The ROS-positive fraction rose from 6.86% to 30.46%; antioxidant co-treatment failed to rescue the phenotype and MG132 did not consistently restore protein markers, arguing against oxidative stress or proteasomal degradation as standalone drivers. Reduced puromycin labeling added a protein-homeostasis readout consistent with reduced nascent protein synthesis. BT-474 and MDA-MB-231 cells showed weaker or different marker responses. Together, these findings define a coordinated MCF-7 response spanning estrogen-associated and cell-cycle programs, survival markers, protein homeostasis, and cell fate.