Cytotoxic and Apoptotic Action of Nonactin and Cephaeline. HBr Precludes Alteration of Redox Status

Background: Natural products or naturally derived compounds are invaluable to human and animal lives either for nutritional value or for medicinal purposes. Indeed, natural products including extracts containing polychemical mixtures play a leading role in the discovery and development of drugs. However, the increasing interest in natural medicines is also attracting a growing concern about the safety of naturally derived medications. Objective: In the present study, we evaluated several naturally derived compounds for in vitro cytotoxicity in mammalian cells. Methods: A total of 54 compounds were evaluated for in vitro cytotoxic and apoptotic action in Human Fibroblast Foreskin (HFF) cells. Results: Of the 54 natural compounds screened for cellular toxicity, only nonactin and cephaeline. HBr reduced cellular viability by ≥60% with IC50 value <3 μg/ml. Addition of trolox antioxidant to the assay medium failed to abate cellular toxicity by both nonactin and cephaeline.HBr treatments. Fluorescence evaluation for Reactive Oxygen Species (ROS) production as well as Mitochondrial Membrane Potential (MMP) was negative for both nonactin and cephaeline.HBr treatments. In contrast, both nonactin and cephaeline.HBr caused cellular apoptosis and this was not attenuated even in the presence of trolox. Conclusion: Taken together, we show evidence supporting that cytotoxic and apoptotic action of nonactin and cephaeline.HBr precludes oxidative stress or ROS production.