In situ monitoring of cell adhesion kinetics using label‐free optical biosensors: Evaluating anticancer potential and selectivity of natural compounds

Abstract The limitations of conventional techniques hinder the identification of natural compounds with anticancer potential in terms of speed, throughput, sensitivity, and the capability of continuous monitoring of relevant biological effects. Novel label‐free optical biosensors represent new opportunities in the discovery of drug candidates, eliminating these difficulties. Our study monitored the anti‐adhesive effects of 11 isolated pure natural compounds (representing four different structural frameworks) and four crude extracts, obtained from plant and fungal sources. The resonant waveguide grating (RWG) method (using an evanescent field‐based label‐free optical biosensor) and a combined miniaturized holographic microscope technique were applied to investigate the effects of pure compounds and crude extracts on cancerous (HeLa) and healthy (preosteoblast) model cells in real time. The adhesion kinetics on fibronectin‐coated surfaces and the morphological parameters on polystyrene surfaces were studied using these model cells in the presence and absence of compounds and extracts. The introduced biosensor method also investigated their interaction with the fibronectin surface. This methodology enables continuous, high‐sensitivity parallel measurements, facilitating the identification of natural compounds with anticancer potential while also providing insights into their mechanism of action. The interaction of the aryltetralin lignans deoxypodophyllotoxin and angeloyl podophyllotoxin with fibronectin was confirmed as a key mechanism behind their non‐selective anti‐adhesive effects. In contrast, the selective adhesion inhibitory effects of the neolignan balanophonin and the alkaloid vermelhotin against HeLa cells were unrelated to fibronectin interaction.