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Injection of Syngeneic Murine Melanoma Cells to Determine Their Metastatic Potential in the Lungs
Published on: May 24, 2016
Effects of VM-26 and lonidamine on a B16 melanoma cell line
A Bellelli1, L Bellelli, M Di Palma
1Laboratory of Physiopathology, Regina Elena National Cancer Institute, Rome, Italy.
Abstract:
The treatment of exponentially-growing B16 melanoma cells with teniposide causes a dose- and time-dependent decrease of cell survival. By means of the nucleoid technique, the formation of double strand breaks was demonstrated in the nuclei of the treated cells, indicating a possible involvement of topoisomerase II. DNA double strand breaks were rapidly but ineffectively repaired. Morphometric and densitometric analyses showed that teniposide treatment causes a considerable increase of nuclear area, nuclear DNA and cell size, associated with a lowering of the mitotic index to less than one hundredth of that of the controls. The cytocidal effect of VM-26 can be potentiated by the addition of a non-lethal dose of lonidamine, whose synergism is particularly evident at low teniposide concentrations.
Insights
Teniposide (VM-26) reduces melanoma cell survival by causing DNA double-strand breaks, which are poorly repaired. Combining teniposide with lonidamine enhances its cell-killing effects, particularly at lower doses.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- B16 melanoma is an aggressive skin cancer.
- Teniposide (VM-26) is a chemotherapeutic agent.
- Topoisomerase II is a key enzyme in DNA replication and repair.
Purpose of the Study:
- To investigate the effects of teniposide on B16 melanoma cell survival.
- To elucidate the mechanism of teniposide-induced cytotoxicity.
- To evaluate the synergistic effect of lonidamine with teniposide.
Main Methods:
- Cell culture of exponentially-growing B16 melanoma cells.
- Nucleoid technique to detect DNA double-strand breaks.
- Morphometric and densitometric analyses.
- Assessment of cell survival and mitotic index.
- Combination treatment with teniposide and lonidamine.
Main Results:
- Teniposide caused a dose- and time-dependent decrease in cell survival.
- DNA double-strand breaks were observed, suggesting topoisomerase II involvement.
- Breaks were rapidly but ineffectively repaired.
- Teniposide increased nuclear area, DNA content, and cell size, while decreasing the mitotic index.
- Lonidamine potentiated teniposide's cytocidal effect, especially at low VM-26 concentrations.
Conclusions:
- Teniposide induces DNA damage and inhibits cell proliferation in B16 melanoma.
- Ineffective DNA repair contributes to teniposide's cytotoxicity.
- Combination therapy with lonidamine offers a potential strategy for enhanced melanoma treatment.
