Quantifying antiproliferative effects of quinolinic acid on melanoma, macrophage and keratinocyte cells using a parametric cell-viability model

Abstract

This paper presents a robust mathematical framework for quantifying antiproliferative effects from noisy in vitro cell viability experiments. The methodology is demonstrated using crystal violet assay measurements of quinolinic acid-induced growth inhibition in B16-F10 murine melanoma, RAW264.7 macrophage, and HaCaT keratinocyte cells through parametric cell viability models. Experimental data exhibited substantial variability and violated the independence assumptions underlying classical inferential statistics. To address these challenges, the proposed framework combines minimal statistical analysis, comprising model-free confidence intervals and pooled within-replicate variability, with deterministic approximation based on least-squares fitting to experimental means and leave-one-replicate-out cross-validation. While all three cell types were described by a common mechanistic framework, each required a distinct parameterisation to capture its characteristic response to quinolinic acid. The resulting one- and two-parameter models accurately described dose- and time-dependent inhibition, with predictive errors close to the intrinsic experimental variability. The models also yielded explicit expressions for time-dependent IC50 values, enabling reliable prediction of inhibitor concentrations required to achieve specified levels of growth inhibition. The proposed framework provides a practical and robust approach for analysing noisy preclinical cell viability data and can be readily extended to other antiproliferative agents and experimental systems.