Can a drug have two different IC50 values in two different cell lines. Please guide?
Yes, it is completely possible. Actually this is a very common and usual situation one and the same drug to have different IC50 in different cells lines. Why? Because of the so called “cell specific response”. Each cell line is a completely unique system, with its individual biological characteristics - even when cell lines were established from the same tissue, species, histologigal type of tumor they differ. What is the reason? The causes are various and include: individual characteristics of the material from which the cell lines were established, heterogeneity of tumor cells (high mutational ability of tumor cells, the continuous appearance and selection of new cell populations in the tumor - as a result, each tumor/tumor cell line is completely unique), the changes occurring in the cells in the course of their cultivation in laboratory conditions… Something more, IC50 can be different also when you evaluate the influence of one and the same drug in one and the same cell line but using different cytotoxicity assays (The assays like MTT test, neutral red uptake cytotoxicty assay, trypan blue dye exclusion technique, crystal violet staining. LDH assay etc have different molecular/cellular targets and mechanisms of action). When performing such type of experiments using different cell lines as model systems you can prepare hierarchical lines – you can grade the cell lines according to their sensitivity/resistance to the cytotoxic effect of the drug (according to the IC50). Good luck!
Thanks Dr. Radostina. This helps a lot. I did observe such trend, and was quite baffled.
I share at 100% Radostina's response.
A quick look on the US NCI website reveals that >30% of the anticancer drugs they have analyzed display GI50 concentrations varying by 2 to 4 magnitudes within the NCI 60-cancer-cell-line panel.
Best regards
Robert
Yes it can. I read a paper about this in regard to withaferin. They report that in MDA-MB-231 cells, the IC-50 value is at 1 micromolar, and for MCF-7 cells the IC-50 value is 2 micro molar. It makes sense that this would be possible seeing that different cell lines have different characteristics and aggressiveness.
I am also getting varying response in different cell lines. I thought it has protocol issue but thanx this discussion was helpful @ Robert Chris
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