Abstract
Background
Osteosarcoma is a prevalent bone cancer in children and adolescents, posing significant treatment challenges due to its propensity for metastasis and resistance to traditional chemotherapy. Gambogic Acid (GA) has been studied for its potential anticancer effects, including inhibition of cell proliferation and induction of apoptosis.
Methods
This study evaluated the effects of GA on osteosarcoma cell lines 143B and U2OS. We conducted cell viability assays, proliferation tests, and wound healing assays to assess the impact of GA on tumor cell behavior. Additionally, molecular analyses including RNA sequencing and RT-qPCR were performed to examine changes in gene expression, specifically focusing on the tumor suppressor transcription factor FOXO3a. We also explored the consequences of FOXO3a knockdown to understand its role in GA's mechanism of action.
Results
GA treatment significantly reduced cell viability and inhibited cell proliferation in both 143B and U2OS cell lines. It also hindered cell migration, demonstrating its potential to impede cancer cell dissemination. Molecular analysis revealed a significant upregulation of FOXO3a following GA treatment, highlighting its crucial role in mediating GA’s anticancer effects. Knockdown studies indicated that the absence of FOXO3a reduced the efficacy of GA, confirming the importance of this transcription factor in GA’s antitumor activity.
Conclusions
The findings from this study suggest that GA, with its low toxicity profile, could serve as a viable alternative to conventional chemotherapy for osteosarcoma treatment. GA's ability to regulate tumor suppressor pathways, particularly through the modulation of FOXO3a, offers new insights into potential cancer treatment strategies using natural compounds. Further research is needed to elucidate the interactive mechanisms between GA and FOXO3a and to develop more effective therapeutic modalities based on this interaction.