Polyphenols from Pennisetum glaucum grains induce MAP kinase phosphorylation and cell cycle arrest in human osteosarcoma cells

Osteosarcoma is the most common bone tumor with a high prevalence among children and adolescents. Polyphenols are widely investigated for their chemopreventive and chemotherapeutic proprieties. In the present study, we explored the pro-apoptotic effects of pearl millet, Pennisetum gloomily phenolic compounds (PGPC) on osteosarcoma U-2OS cells. Our results show that PGPC induced U-2OS cells death, in a dose dependent manner, with an IC50 of 80 mu g/mL. Annexin-V and 7-AAD staining show that PGPC induced cell death mainly through caspase-dependent apoptosis as shown by a decrease in cell death when co-treated with pan-caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk). PGPC caused an increase in cytoplasmic calcium associated with caspases activation and poly (ADP-ribose) polymerase PARP cleavage. Western blot analysis revealed that PGPC upregulated p38 MAPK and SAPK/JNK activity and inhibited c-SRC/AKT pathway. Finally, cell cycle analysis shows that PGPC decreased CDK2 and increased cyclin E expression, resulting in U-2OS cells accumulation in S phase. These results demonstrate that PGPC induce p38 MAPK and SAPK/JNK activation, and attenuate AKT activation, leading to cell cycle arrest and apoptosis in osteosarcoma U-2OS cells.