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Analysis of proliferation and apoptotic induction by 20 steroid glycosides in 143B osteosarcoma cells in vitro
C I Delebinski1, S Georgi2, S Kleinsimon1
1Department of Paediatric Oncology/Haematology, Otto-Heubner-Centre for Paediatric and Adolescent Medicine (OHC), Charité, Universitaetsmedizin Berlin, Berlin, 13353, Germany.
Objectives:
Osteosarcoma is the most common type of malignant bone tumour in children and adolescents; it has poor prognosis, is highly metastatic and is resistant to current therapeutic approaches. In this study, different herbal extracts used in phytotherapy have been screened after searching innovative natural anti-cancer components.
Materials And Methods:
Twenty steroid glycosides were examined for accordance to their potential of inhibiting cell proliferation and inducing apoptosis in the osteosarcoma cell line 143B. Cell proliferation was examined using a CASY counter. Effects of cardiac glycosides on induction of apoptosis were evaluated by Annexin V-APC and flow cytometry, caspase activity assay and measurement of mitochondrial membrane potential.
Results:
The study revealed that various steroid glycosides suppress cell proliferation in a concentration-dependent manner. Further investigations indicated apoptotic induction by 17 of the 20 tested cardenolides and bufadienolides. Bufadienolide proscillaridin A, arenobufagin, and cardenolides evomonoside, convallatoxol and ouabain waged strongest apoptotic induction, associated with breakdown of mitochondrial membrane potential and activation of caspases -8 and -9. In contrast, the bufadienolide resibufogenin and cardenolide uzarin had no effect on proliferation inhibition, apoptotic induction or change in mitochondrial membrane potential.
Conclusion:
These results indicate that bufadienolides proscillaridin A and arenobufagin and cardenolide evomonoside, or related natural compounds might be promising new starting points for development of novel anti-cancer agents for treatment of osteosarcoma.
Insights
Certain steroid glycosides show potential as new treatments for osteosarcoma, a common childhood bone cancer. These natural compounds effectively inhibit cancer cell growth and induce apoptosis, offering hope for novel anti-cancer therapies.
Area of Science:
- Oncology
- Pharmacology
- Natural Products Chemistry
Background:
- Osteosarcoma is a prevalent and aggressive bone cancer in children and adolescents with limited treatment options.
- Current therapies for osteosarcoma often face challenges due to poor prognosis, high metastatic potential, and therapeutic resistance.
- Phytotherapy offers a promising avenue for discovering novel anti-cancer agents derived from natural sources.
Purpose of the Study:
- To screen various herbal extracts for novel anti-cancer components.
- To evaluate the potential of twenty steroid glycosides in inhibiting osteosarcoma cell proliferation and inducing apoptosis.
- To identify specific compounds with significant anti-cancer activity against the 143B osteosarcoma cell line.
Main Methods:
- Steroid glycosides were tested for their effects on the 143B osteosarcoma cell line.
- Cell proliferation was quantified using a CASY counter.
- Apoptosis induction was assessed via Annexin V-APC staining, flow cytometry, caspase activity assays, and mitochondrial membrane potential measurements.
Main Results:
- Multiple steroid glycosides demonstrated a concentration-dependent suppression of osteosarcoma cell proliferation.
- Seventeen out of twenty tested cardenolides and bufadienolides successfully induced apoptosis.
- Proscillaridin A, arenobufagin, evomonoside, convallatoxol, and ouabain exhibited the strongest apoptotic induction, linked to mitochondrial dysfunction and caspase activation.
Conclusions:
- Bufadienolides (proscillaridin A, arenobufagin) and cardenolides (evomonoside) show significant potential as starting points for new osteosarcoma treatments.
- These natural compounds may lead to the development of novel anti-cancer agents for osteosarcoma therapy.
- Further research into related natural compounds could yield effective therapeutic strategies for osteosarcoma.
