Antagonistic L1 Adhesion Molecule Mimetic Compounds Inhibit Glioblastoma Cell Migration In Vitro

Biomolecules, 2022 · DOI: https://doi.org/10.3390/biom12030439 · Published: March 12, 2022

Simple Explanation

Cell adhesion molecule L1, which usually helps nerve cells migrate and regenerate, can also help tumor cells migrate and spread. This study looked at compounds that can block L1's function in tumors. Researchers screened small organic compounds to find ones that would inhibit L1's function, focusing on reducing tumor cell migration. They identified three compounds—anagrelide, 2-hydroxy-5-fluoropyrimidine, and mestranol—that can inhibit tumor cell migration in a way that depends on L1. This raises hopes for potential cancer therapies.

Study Duration

96 h

Participants

U251 human glioblastoma cells, OVCAR3 human ovarian cancer cells, A172 glioblastoma cell line, HEK293T human embryonic kidney cells

Evidence Level

In vitro study

Key Findings

1
Anagrelide, 2-hydroxy-5-fluoropyrimidine, and mestranol competitively inhibit antibody 324 binding to L1, suggesting they interfere with L1's function.
2
These compounds are not toxic to U251 cells at concentrations up to 100 µM, making them potentially safe for therapeutic use.
3
The mimetics inhibit migration of U251 cells, and this inhibition is L1 dependent.

Research Summary

This study identifies three L1 antagonistic mimetics—anagrelide, 2-hydroxy-5-fluoropyrimidine, and mestranol—that inhibit the migration of cultured tumor cells in an L1-dependent manner. The mimetics competitively inhibit the binding of antibody 324 to L1 and bind to L1 in a homophilic manner. The inhibition of tumor cell migration by these mimetics is L1-dependent, as demonstrated by experiments using L1-silenced cells.

Practical Implications

Cancer Therapy

The identified L1 antagonistic mimetics may be useful for therapy of a wide variety of cancers.

Drug Repurposing

Since all L1 antagonistic drugs reported here have known toxicological and pharmacokinetic proﬁles, their repurposing would thus reduce the need for the establishment of a fully new therapeutic proﬁle.

Further Research

In vivo experiments will have to be performed to evaluate the effects of the three mimetics on tumors of mouse and human origins.

Study Limitations

1
The discovered compounds impact non-tumor-related functions.
2
Effects on estrogen receptors need to be considered in the case of mestranol.
3
The concentrations needed to reduce tumor cell migration may be different from those affecting other cell types.

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