Analysis of proliferation and apoptotic induction by 20 steroid glycosides in 143B osteosarcoma cells in vitro.

OBJECTIVE

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.

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.

CONCLUSIONS

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.