Trustworthiness of IC50 values
I have worked in natural product isolation a little. Although I have never witnessed tests with HeLa cells, I can provide some insight into the general screening procedure.

In the lab I worked in which dealt with isolation of myxobacterial natural products, a novel strain was first tested as a crude extract in a preliminary screening via serial dilution assay. Tests were performed against a set of standard screening organisms including S. aureus, Candida albicans, E. coli and a few others I forgot.

If an isolated showed enough inhibitory activity at this stage, a semipreparative HPLC was performed to locate the peak(s) which caused said activity. The HPLC fractions were collected in a 96-well plate, the solvent removed by nitrogen flow and then the well plate was infected with the organism of interest. Hopefully, one or two wells would remain with out bacterial or fungal growth and hopefully these would not be in the fatty acid realm at the end of the 96 wells.

After that, a slightly larger separation was performed with the goal of gaining a few milligrams of the active compound (after confirming via HR-MS and dereplication that it was not already known) to perform another serial dilution assay to identify the minimal inhibitory concentration (MIC) — the isolationists’ equivalent to an $\mathrm{LD_{50}}$. This was typically performed around three times.

After that, the paper was drafted and submitted to peer review.

(Okay, there are a few steps I left out, but they contain other, unrelated stuff like making sure the myxobacterium was properly classified, elucidating the structure, hoping for crystals and maybe even performing some low-scale fermentation of the relevant myxobacteria to gain enough sample for proper structure elucidation. Ths last step could also preceed the MIC value determination.)