NK-1 Receptor Blocker Aprepitant Kills Cancer Cells but Also Harms Normal Cells — Peptide Alternative Falls Short
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- Not selective Aprepitant was equally toxic to cancer and normal cell lines, contradicting previous claims of cancer selectivity
- Evidence Grade:
- Low-moderate — well-designed comparative study but limited by in vitro methodology and small cell line panel.
- Study Age:
- Published in 2020; NK-1R as a cancer target remains debated.
- Original Title:
- 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.
- Published In:
- Folia neuropathologica, 58(3), 237-244 (2020)
- Database ID:
- RPEP-04987
Evidence Hierarchy
Frequently Asked Questions
Could anti-nausea drugs treat cancer?
Aprepitant (used for chemotherapy nausea) kills cancer cells in lab tests, but this study found it equally kills normal cells — meaning it's likely not a targeted cancer treatment.
Why didn't the peptide antagonist work well?
The peptide version was much less potent than the small molecule aprepitant, only showing effects at very high concentrations that may not be achievable in the body.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-04987APA
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
MLA
Matalińska, Joanna, et al. "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, 2020. https://doi.org/10.5114/fn.2020.100066
RethinkPeptides
RethinkPeptides Research Database. "Antiproliferative effects of [D-Pro2, D-Trp7,9]-Substance P ..." RPEP-04987. Retrieved from https://rethinkpeptides.com/research/matalinska-2020-antiproliferative-effects-of-dpro2
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.