The anti-nausea drug aprepitant potently reduced cancer cell proliferation but was equally toxic to normal cells, while the peptide NK-1 antagonist showed minimal anticancer activity.
Not selectiveAprepitant was equally toxic to cancer and normal cell lines, contradicting previous claims of cancer selectivity
What the researchers found
Aprepitant potently reduced cancer cell proliferation but was not selective (equally toxic to normal cells); the peptide NK-1 antagonist showed minimal anticancer activity even at 100 µM.
Why it matters
Challenges the idea that NK-1 receptor blockers are selective cancer treatments. Aprepitant's lack of selectivity limits its potential as an anti-cancer drug despite strong antiproliferative effects.
The numbers in context
Aprepitant potent in all 5 cancer lines but also in 3 normal lines; peptide antagonist effective only at 100 uM in few lines; no colony formation effect
How the study worked
In vitro: 5 cancer + 3 normal cell lines; cell proliferation test, MTT assay, and colony formation assay; aprepitant vs [D-Pro2, D-Trp7,9]-Substance P at multiple concentrations.
Who was studied
5 cancer cell lines and 3 normal cell lines treated with aprepitant or [D-Pro2,D-Trp7,9]-Substance P
What this study cannot tell us
In vitro only; limited cell line panel; peptide antagonist concentrations may not be pharmacologically relevant; aprepitant's non-selectivity may be dose-dependent.
How to read the evidence
Low-moderate — well-designed comparative study but limited by in vitro methodology and small cell line panel.
When this study was published
Published in 2020; NK-1R as a cancer target remains debated.
The bigger picture
The substance P/NK-1R cancer connection generated excitement, but this study suggests the anticancer effects of NK-1 antagonists may be non-specific cytotoxicity rather than targeted anti-cancer action.
Questions still open
- Are the anticancer effects of aprepitant NK-1R-mediated or due to off-target cytotoxicity?
- Could lower, clinically achievable aprepitant concentrations show cancer selectivity?
- Are there other NK-1R antagonists with better selectivity profiles?
Common questions
Could anti-nausea drugs treat cancer?
Why didn't the peptide antagonist work well?
Read the original research
Antiproliferative effects of [D-Pro2, D-Trp7,9]-Substance P and aprepitant on several cancer cell lines and their selectivity in comparison to normal cells.
Folia neuropathologica, 58(3), 237-244
Citation
Matalińska, Joanna; Świć, Agnieszka; Lipiński, Piotr; Misicka, Aleksandra. (2020). Antiproliferative effects of [D-Pro2, D-Trp7,9]-Substance P and aprepitant on several cancer cell lines and their selectivity in comparison to normal cells.. Folia neuropathologica, 58(3), 237-244. https://doi.org/10.5114/fn.2020.100066