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Updated: Sep 29, 2025

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Multiple Effects of Resveratrol on Osteosarcoma Cell Lines
Angela De Luca1, Daniele Bellavia1, Lavinia Raimondi1
1IRCCS Istituto Ortopedico Rizzoli, CS Surgical Sciences and Technologies-SS Omics Science Platform for Personalized Orthopedics, 40136 Bologna, Italy.
Abstract:
Osteosarcoma (OS) is the most common primary bone sarcoma affecting the life of pediatric patients. The clinical treatment faces numerous difficulties, including the adverse effects of chemotherapies, chemoresistance, and recurrences. In this study, the effects of resveratrol (RSV), a natural polyphenol, on OS cell lines were investigated to evaluate its action as an adjuvant therapy to the current chemotherapy regimens. RSV exhibited multiple tumor-suppressing activities on OS cell lines, inducing a series of critical events. We found (1) a cell growth inhibition due to an increase in cell distress, which was, in part, due to the involvement of the AKT and caspase-3 pathways, (2) an increase in cellular differentiation due to major gene expression levels of the osteoblastic differentiation genes, (3) an inhibition of IL-6 secretion due to an epigenetic effect on the IL-6 promoter, and (4) an inhibition of OS cells migration related to the decrease in IL-8 secretion levels due to an epigenetic effect on its promoter. Finally, the cotreatment of RSV with doxorubicin and cisplatin increased their cytotoxic effect on OS cells. Although further investigations are mandatory, it seems RSV might be a promising therapeutic adjuvant agent for OS cell treatment, exerting an antitumor effect when combined with chemotherapy.
Insights
Resveratrol (RSV) shows promise as an adjuvant therapy for osteosarcoma (OS). This natural compound inhibits OS cell growth and migration while enhancing chemotherapy
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Osteosarcoma (OS) is a prevalent bone cancer in children, presenting treatment challenges like chemoresistance and recurrence.
- Current chemotherapy regimens for OS have limitations, including adverse effects and limited efficacy.
Purpose of the Study:
- To investigate the potential of resveratrol (RSV), a natural polyphenol, as an adjuvant therapy for osteosarcoma.
- To evaluate the anti-tumor effects of RSV on OS cell lines, both alone and in combination with standard chemotherapies.
Main Methods:
- In vitro studies on osteosarcoma cell lines treated with resveratrol.
- Analysis of cell growth, differentiation markers, apoptosis pathways (AKT, caspase-3), and cytokine secretion (IL-6, IL-8).
- Investigation of epigenetic modifications on IL-6 and IL-8 promoter regions.
Main Results:
- Resveratrol demonstrated significant tumor-suppressing activities, including inhibition of cell growth and migration.
- RSV treatment led to increased osteoblastic differentiation and modulated apoptosis pathways.
- Epigenetic effects on IL-6 and IL-8 promoters were observed, reducing their secretion.
- Combination therapy of RSV with doxorubicin and cisplatin enhanced cytotoxic effects on OS cells.
Conclusions:
- Resveratrol exhibits multiple anti-cancer properties against osteosarcoma cells.
- RSV shows potential as a therapeutic adjuvant, enhancing the efficacy of conventional chemotherapy for osteosarcoma.
- Further research is warranted to explore RSV's clinical application in osteosarcoma treatment.

