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Updated: Aug 21, 2026
Three-Dimensional In Vitro Biomimetic Model of Neuroblastoma Using Collagen-Based Scaffolds
Published on: July 9, 2021
In vitro toxicity of bisphosphonates on human neuroblastoma cell lines
Marta Vorotnjak1, Joachim Boos, Claudia Lanvers-Kaminsky
1University Children's Hospital, Department of Pediatric Hematology and Oncology, Münster, Germany.
Abstract:
Neuroblastoma is the commonest extracranial solid tumor of childhood and frequently metastasizes to the bone. Bisphosphonates are standard treatment of osteolytic lesions by bone metastasis. Since recent studies suggested direct antitumor effects of bisphosphonates, we screened the toxicity of different bisphosphonates on neuroblastoma cell lines. The nitrogen-containing bisphosphonate pamidronate was significantly more toxic on a panel of eight neuroblastoma cell lines than the non-nitrogen-containing bisphosphonates, clodronate and tiludronate. After 72 h, GI50 concentrations (inhibiting cell growth by 50% compared to untreated controls) for pamidronate ranged from 12.8 to >500 microM. CHLA-90 and SH-SY5Y were the most sensitive cell lines. In CHLA-90, zoledronate was the most cytotoxic bisphosphonate, followed by alendronate, pamidronate and ibandronate. In SH-SY5Y, alendronate was the most cytotoxic bisphosphonate, followed by ibandronate, pamidronate and zoledronate. The GI50 values after 72 h were 34.1 (SH-SY5Y) and 3.97 microM (CHLA-90) for zoledronate, and 22.4 (SH-SY5Y) and 9.55 microM (CHLA-90) for alendronate. Neuroblastoma cells treated with bisphosphonates showed signs of differentiation and finally underwent apoptosis. The observed GI50 concentrations suggest that local nitrogen-containing bisphosphonate concentrations at the bone interface can directly target neuroblastoma cell penetration into the bone matrix. In summary, these observations warrant the investigation of adjuvant bisphosphonate treatment in controlled clinical trials.
Insights
Nitrogen-containing bisphosphonates show direct antitumor effects against neuroblastoma cells, inducing differentiation and apoptosis. This suggests potential for adjuvant bisphosphonate therapy in clinical trials for bone metastasis.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Neuroblastoma is a common pediatric extracranial solid tumor with frequent bone metastasis.
- Bisphosphonates are standard treatments for osteolytic bone lesions.
- Emerging evidence suggests bisphosphonates may possess direct antitumor properties.
Purpose of the Study:
- To screen the toxicity of various bisphosphonates on neuroblastoma cell lines.
- To compare the efficacy of nitrogen-containing versus non-nitrogen-containing bisphosphonates.
- To evaluate the potential of bisphosphonates as an adjuvant therapy for neuroblastoma.
Main Methods:
- Screening of bisphosphonate toxicity on eight neuroblastoma cell lines.
- Determination of GI50 concentrations for different bisphosphonates after 72 hours.
- Assessment of cellular differentiation, apoptosis, and drug effects at the bone interface.
Main Results:
- Nitrogen-containing bisphosphonates, particularly pamidronate, demonstrated significantly higher toxicity than non-nitrogen-containing agents.
- Zoledronate and alendronate were the most cytotoxic in sensitive cell lines (CHLA-90 and SH-SY5Y, respectively).
- Bisphosphonate treatment induced neuroblastoma cell differentiation and apoptosis, with effective concentrations at the bone interface.
Conclusions:
- Nitrogen-containing bisphosphonates exhibit direct cytotoxic effects on neuroblastoma cells.
- The findings support the investigation of bisphosphonates for targeting neuroblastoma bone metastasis.
- Adjuvant bisphosphonate therapy warrants further evaluation in controlled clinical trials.
