Epidermal growth factor can induce apoptosis in neuroblastoma.
OBJECTIVE
In previous studies, incubation of doxorubicin-resistant neuroblastoma SK-N-SH (Dox-R) cells with epidermal growth factor (EGF) decreased extracellular signal-regulated kinase activation. Because extracellular signal-regulated kinase activation is associated with cell proliferation, we hypothesized that EGF could induce apoptosis and decrease the rate of cell growth in these cells.


METHODS
The growth of wild-type (WT) SK-N-SH and Dox-R cells after incubation with EGF concentrations ranging from 1 to 100 ng/mL was determined by a colorimetric assay. Apoptosis was assessed by Hoechst staining and DNA laddering in WT, Dox-R, and cisplatin-resistant cells treated with EGF (100 ng/mL). Cleaved caspase-3 and EGF receptor (human epidermal growth factor receptor [HER1-HER4]) expression were verified by Western blot and reverse transcriptase-polymerase chain reaction.


RESULTS
Epidermal growth factor decreased WT cell growth at concentrations between 50 and 100 ng/mL; Dox-R cell growth was attenuated at all EGF concentrations. Apoptosis was observed in WT and Dox-R cells incubated with EGF. Maximal cleaved caspase-3 expression occurred in WT cells treated with EGF 100 ng/mL and in Dox-R treated with EGF 5 to 10 ng/mL. Epidermal growth factor did not induce apoptosis in cisplatin-resistant cells. HER2 and HER3 transcription was maximal in WT and Dox-R cells, respectively.


CONCLUSIONS
Wild-type and Dox-R cells exhibited decreased cell growth after EGF treatment because of apoptosis. This involved caspase-3 activation and could work through HER2 and HER3 receptors.
Chiu
Bill
B
Department of Surgery, Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL 60614, USA.
Mirkin
Bernard
B
Madonna
Mary Beth
MB
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D009447:Neuroblastoma
D000970:Antineoplastic Agents; D004815:Epidermal Growth Factor