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Human myeloma cell apoptosis induced by interferon-alpha
T Otsuki1, O Yamada, H Sakaguchi
1Department of Hygiene, Kawasaki Medical School, Okayama, Japan.
Abstract:
Although there have been reports regarding the clinical effectiveness of IFN alpha in the treatment of myeloma patients during this decade, its biological effects on human myeloma cells have still not been clarified. Recently, apoptosis has been considered as one of the most important mechanisms in the programmed cell death of malignant tumour cells induced by chemotherapeutic agents or cytotoxic immunological defence in malignancy-carrying hosts. Among the several pathways which function to induce apoptosis, Fas and the Fas ligand system have been thought to play an important role in inducing tumour-cell apoptosis, particularly in immunological prevention. In this study we investigated myeloma cell apoptosis induced by IFN alpha using five human myeloma cell lines which were established without any additional supplementation of IL-6. In addition, the mRNA expression levels of apoptosis-related genes employing the reverse transcriptase-polymerase chain reaction (RT-PCR) were also analysed with the KMS-12-PE cell line, which was the most sensitive of the five cell lines in terms of apoptosis induced by IFN alpha. Based on the results, it was determined that IFN alpha induced myeloma cell apoptosis in a dose-dependent manner, but the sensitivity to IFN alpha in the cell lines examined varied and one cell line revealed growth stimulation by IFN alpha. In addition, the apoptosis induced by IFN alpha did not seem to be mediated by the Fas/Fas ligand pathway. Finally, the IL-6, IL-6R, IRF1 and IRF2 genes were up-regulated in KMS-12-PE cells cultured with IFN alpha. Therefore these genes may play an important role during apoptosis induced by IFN alpha.
Insights
Interferon alpha (IFN alpha) induces myeloma cell apoptosis in a dose-dependent manner, but not via the Fas/Fas ligand pathway. Specific genes like IL-6 and IRF1 are upregulated, suggesting their role in IFN alpha-induced apoptosis.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Clinical effectiveness of Interferon alpha (IFN alpha) in myeloma treatment is reported, yet its biological impact on myeloma cells remains unclear.
- Apoptosis, or programmed cell death, is crucial for eliminating malignant tumor cells, with the Fas/Fas ligand system implicated in immune-mediated tumor cell apoptosis.
Purpose of the Study:
- To investigate the mechanisms of IFN alpha-induced apoptosis in human myeloma cell lines.
- To analyze the expression of apoptosis-related genes in response to IFN alpha treatment.
Main Methods:
- Five human myeloma cell lines were used to assess IFN alpha-induced apoptosis.
- Reverse transcriptase-polymerase chain reaction (RT-PCR) was employed to analyze mRNA expression of apoptosis-related genes in the KMS-12-PE cell line.
Main Results:
- IFN alpha induced myeloma cell apoptosis in a dose-dependent manner, with varying sensitivity across cell lines; one cell line exhibited growth stimulation.
- Apoptosis induced by IFN alpha was not mediated through the Fas/Fas ligand pathway.
- Upregulation of IL-6, IL-6R, IRF1, and IRF2 genes was observed in KMS-12-PE cells treated with IFN alpha.
Conclusions:
- IFN alpha can induce apoptosis in human myeloma cells, but the response varies.
- The Fas/Fas ligand pathway is not the primary mediator of IFN alpha-induced apoptosis in these cells.
- Upregulated genes including IL-6, IL-6R, IRF1, and IRF2 may play significant roles in IFN alpha-mediated apoptosis.