AI Article Synopsis
- Erufosine, an injectable compound, shows strong anti-cancer effects on multiple myeloma (MM) cell lines, with its cytotoxicity linked to varying apoptotic and non-apoptotic mechanisms across different cell types.
- The study demonstrated that erufosine's effectiveness in inducing cell death inversely correlates with the level of Bcl-X(L) protein and highlights its ability to inhibit cell migration and enhance the effects of other drugs.
- Importantly, erufosine was not harmful to normal hematopoietic progenitor cells and even stimulated the growth of certain blood cell colonies, suggesting its potential as a safe and effective treatment for multiple myeloma.
Article Abstract
Purpose: Erufosine is an i.v. injectable alkylphosphocholine which is active against various haematological malignancies in vitro. In the present study, its effects on multiple myeloma (MM) cell lines and on murine and human hematopoietic progenitor cells (HPCs) were investigated.
Methods: The following MM cell lines were used: RPMI-8226, U-266 and OPM-2. The cytotoxicity of erufosine against these cell lines was determined by the MTT-dye reduction assay. Bcl-2, Bcl-X(L) and pAkt expression levels, activation of caspases, as well as cleavage of PARP, were studied by Western blotting. Migration was evaluated by a modified Boyden-chamber assay. The haematologic toxicity of erufosine was assessed using clonogenicity assays with normal HPCs of murine or human origin.
Results: Significant cytotoxic activity of erufosine against the MM cell lines was found. Comparison of the characteristics of erufosine-induced cell death in the three cell lines revealed a complex mode of action with apoptotic mechanisms prevailing in OPM-2 cells and non-apoptotic mechanisms prevailing in U-266 cells. The sensitivity of the MM cell lines to erufosine-induced apoptosis correlated inversely with the Bcl-X(L) expression level. Erufosine participated in synergistic interactions with various drugs. Furthermore, it showed potent migration-inhibiting activity in RPMI-8226 cells. Erufosine was not toxic to normal HPCs of murine or human origin and even stimulated progenitors from human umbilical cord blood to form granulocyte/macrophage colonies. Moreover, erufosine ameliorated the toxicity of bendamustine to murine HPCs.
Conclusions: Overall, the data presented reveal that erufosine could have potential as an antimyeloma drug and deserves further development.
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| http://dx.doi.org/10.1007/s00280-010-1273-5 | DOI Listing |
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