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Interferon-alpha induces apoptosis in human KB cells through a stress-dependent mitogen activated protein kinase
M Caraglia1, A Abbruzzese, A Leardi
1Dipartimento di Biochimica e Biofisica 'F. Cedrangolo', Il Università di Napoli, Italy.
Abstract:
We have demonstrated that interferon-alpha2-recombinant (IFNalpha) at growth inhibitory concentrations enhances the expression and signalling activity of the epidermal growth factor receptor (EGF-R) in human epidermoid carcinoma KB cells. Here we report that KB cells exposed to IFNalpha underwent apoptotic cell death and this effect was antagonized by EGF. We have also found that IFNalpha enhanced the expression of heat shock proteins (HSP) HSP-70, HSP-90 and HSP-27 and activated the NH2-terminal Jun kinase-1 (JNK-1) and p38 mitogen activated protein kinase, the target enzymes of a stress-dependent intracellular transduction pathway. Moreover, the overexpression of the wild-type JNK-1, obtained through plasmid transfection of KB cells, induced apoptosis which was potentiated by the exposure of wild-type JNK-1 (JNK-1wt)-transfected cells to IFNalpha. All these effects were neutralized by the addition of EGF to parental and JNK-1wt-transfected KB cells exposed to IFNalpha. In conclusion, EGF has a protective effect on KB cells from apoptosis while antagonizing a stress response elicited by IFNalpha and targeted on the stress pathway terminal kinases.
Insights
Interferon-alpha2-recombinant (IFNalpha) induces cancer cell death by activating stress pathways, but epidermal growth factor (EGF) protects cells by antagonizing this response.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Interferon-alpha2-recombinant (IFNalpha) is known to inhibit cell growth.
- Epidermal growth factor receptor (EGF-R) signaling is implicated in cancer cell proliferation.
- Understanding the interplay between IFNalpha and EGF-R is crucial for cancer therapy.
Purpose of the Study:
- To investigate the effect of IFNalpha on apoptosis in human epidermoid carcinoma KB cells.
- To determine the role of epidermal growth factor (EGF) in modulating IFNalpha-induced cellular responses.
- To elucidate the involvement of stress-dependent intracellular pathways in IFNalpha's action.
Main Methods:
- Exposure of KB cells to IFNalpha and EGF.
- Analysis of epidermal growth factor receptor (EGF-R) expression and signaling.
- Assessment of apoptotic cell death.
- Measurement of heat shock protein (HSP) expression.
- Activation analysis of c-Jun N-terminal kinase-1 (JNK-1) and p38 mitogen-activated protein kinase (MAPK).
- Overexpression of JNK-1 via plasmid transfection.
Main Results:
- IFNalpha enhanced EGF-R expression and signaling in KB cells.
- IFNalpha induced apoptotic cell death, which was antagonized by EGF.
- IFNalpha increased the expression of HSP-70, HSP-90, and HSP-27.
- IFNalpha activated JNK-1 and p38 MAPK pathways.
- Overexpression of JNK-1 potentiated IFNalpha-induced apoptosis.
- EGF neutralized IFNalpha-induced apoptosis and stress responses in both parental and JNK-1 overexpressing cells.
Conclusions:
- EGF exerts a protective effect against IFNalpha-induced apoptosis in KB cells.
- EGF antagonizes the stress response pathway activated by IFNalpha.
- The findings highlight a complex interplay between growth factor signaling and stress response pathways in cancer cells.