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Published on: May 14, 2016
Gentamicin arrests cancer cell growth: the intriguing involvement of nuclear sphingomyelin metabolism
Michela Codini1, Samuela Cataldi2, Francesco Saverio Ambesi-Impiombato3
1Department of Pharmaceutical Science, University of Perugia, Perugia 06122, Italy. codini@virgilio.it.
Abstract:
The use of gentamicin for the treatment of bacterial infection has always been an interesting and highly speculated issue for the scientific community. Conversely, its effect on cancer cells has been very little investigated. We studied the effect of high doses of gentamicin on non-Hodgkin's T-cell human lymphoblastic lymphoma (SUP-T1). We showed that gentamicin delayed cell growth and induced cell death in lymphoma cells with a rather mild effect on lymphocytes. In SUP-T1 cells, GAPDH, B2M, CDKN1A and CDKN1B were down-expressed in comparison with lymphocytes. Gentamicin treatment in SUP-T1 cells restored the expression of GAPDH, B2M and CDKN1A to values similar to those of lymphocytes and caused overexpression of CDKN1B. The drug acted via sphingomyelin metabolism; in whole cells, sphingomyelinase activity was stimulated, whereas in purified nuclei, sphingomyelinase activity was inhibited and that of sphingomyelin-synthase was stimulated, with a consequent high level of nuclear sphingomyelin content. We suggest that the increase of nuclear sphingomyelin might enrich the nucleus of lipid microdomains that act as a platform for active chromatin and, thus, might be responsible for gene expression. It is possible that in lymphoblastic lymphoma, high doses of gentamicin induce a beneficial therapeutic outcome.
Insights
High doses of gentamicin show potential in treating lymphoblastic lymphoma by delaying cancer cell growth and inducing cell death. This antibiotic may offer a novel therapeutic approach for certain cancers.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Gentamicin is primarily used for bacterial infections.
- Its effects on cancer cells, particularly lymphoblastic lymphoma, are largely unexplored.
Purpose of the Study:
- To investigate the impact of high-dose gentamicin on non-Hodgkin's T-cell human lymphoblastic lymphoma (SUP-T1) cells.
- To elucidate the molecular mechanisms underlying gentamicin's effects on these cancer cells.
Main Methods:
- Treatment of SUP-T1 cells and lymphocytes with high-dose gentamicin.
- Analysis of gene expression changes (GAPDH, B2M, CDKN1A, CDKN1B).
- Investigation of sphingomyelin metabolism and its impact on nuclear sphingomyelin content.
Main Results:
- Gentamicin significantly delayed SUP-T1 cell growth and induced cell death.
- Gene expression of GAPDH, B2M, and CDKN1A was restored to lymphocyte levels, while CDKN1B was overexpressed in SUP-T1 cells post-treatment.
- Gentamicin modulated sphingomyelinase and sphingomyelin-synthase activity, increasing nuclear sphingomyelin content.
Conclusions:
- High-dose gentamicin exhibits anti-lymphoma activity by altering gene expression and sphingomyelin metabolism.
- Increased nuclear sphingomyelin may influence chromatin structure and gene expression, contributing to therapeutic effects.
- Gentamicin presents a potential therapeutic strategy for lymphoblastic lymphoma.
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