Method Profile
Compare state-dependent drug potency across tumor model formats and investigate oxidative stress and cell-death pathways in H2228 cells.
Identify activity against growth-restricted tumor cells while retaining model-specific measurements and mechanism evidence.
Human H2228 lung cancer monolayers and spheroids, C45 colorectal cancer organoids and WI-38 fibroblasts.
General-growth conditions are compared with low-oxygen, nutrient-limited quiescent conditions appropriate to each model.
Tumor models
H2228 monolayers, H2228 spheroids and one C45 organoid line.
Pharmacological comparisons
Dequalinium, rotenone and the lipid-peroxidation inhibitor ferrostatin-1.
Cell states
Matched growing and quiescent conditions within each tumor model.
Fit concentration responses separately for each state and model. Attribute detailed ferroptosis experiments to H2228 cells rather than to the C45 organoid comparison.
Within-model cell-state concentration responses with additional mechanism perturbations.
H2228 monolayers and spheroids; one C45 line. Drug-response curves n=5, WI-38 comparison n=3.
Growing and quiescent states, with WI-38 and ferrostatin-1 comparisons.
Quiescent/growing EC50: monolayers 0.29±0.060/2.8±1.1 μM; spheroids 1.6±0.75/23±5.3 μM; C45 organoids 31±7.6/>50 μM. Ferrostatin-1 prevented lipid peroxidation and death in quiescent H2228 cells.
Low-oxygen, nutrient-limited tumor models were more sensitive to dequalinium than actively growing counterparts. Detailed H2228 experiments linked the response to oxidative stress and ferroptotic cell death.
