ReviewThe search for plants with anticancer activity: Pitfalls at the early stages

Inhibition assays on tumour cells in vitro are commonly used to confirm the activity of extracts, fractions and compounds from plants reported to be antitumoural. The majority of assays report the IC50 (50% inhibitory concentration), whereas others distinguish between inhibition of cell proliferation (cytostasis) and cell death (cytotoxicity). Here, we offer some suggestions as to the different types of assay, the cell lines that may be used, control cells and drugs, as well as the interpretation of the results. Using both theoretical considerations and experimental data, we specifically question the frequent overinterpretation of reported results regarding the selectivity for cancer cells of the plant extract or compound under study, concluding that this “selectivity” is due to a quantitative difference in cell proliferation rates, rather than a qualitative difference between normal and tumour cells. Inhibition assays will always represent one of the first steps in the discovery of clinically valuable new drugs, but these assays do not allow us to conclude that we have found the “magic bullet”.

Hypothetical data were generated to yield identical GI50, TGI and LC50 values for fast and slow growing cells. However, when exactly the same results were analysed in terms of the IC50, the faster growing cells appeared to be over 10-fold more sensitive.148