Curcumin and Methotrexate: A Promising Combination for Osteosarcoma Treatment via Hedgehog Pathway Inhibition

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Osteosarcoma (OS) is a severe pediatric bone cancer often treated with toxic chemotherapy.
• The Hedgehog (Hh) signaling pathway is implicated in OS tumorigenesis and is overexpressed in tumors.
• Current therapies for OS have significant acute and chronic side effects, necessitating safer alternatives.

Purpose of the Study:

• To investigate the therapeutic potential of Curcumin (CUR) alone and in combination with Methotrexate (MTX) against the MG-63 OS cell line.
• To evaluate the effects of CUR and MTX on the Hedgehog signaling pathway in OS cells.
• To explore a novel therapeutic strategy for OS with an improved safety profile.

Main Methods:

• Culturing and treating the MG-63 osteosarcoma cell line with CUR and MTX.
• Assessing cell proliferation, apoptosis (BAX/Bcl-2 ratio), and invasion.
• Quantifying the expression levels of Hh pathway components (PTCH1, SMO, GLI1, GLI2) and other signaling molecules (β-Catenin, NF-kB, MMP-2, MMP-9).

Main Results:

• CUR and MTX significantly increased apoptosis and the BAX/Bcl-2 ratio in OS cells.
• Combined treatment downregulated key Hh pathway components (PTCH1, SMO, GLI1, GLI2), inhibiting proliferation, survival, and invasion.
• CUR and MTX reduced β-Catenin expression and showed a trend toward decreasing NF-kB, MMP-2, and MMP-9.

Conclusions:

• Curcumin demonstrates potential as a supportive agent in osteosarcoma treatment, particularly when combined with Methotrexate.
• Targeting the Hedgehog signaling pathway with CUR and MTX offers a promising strategy to enhance therapeutic outcomes and reduce the toxicity of conventional OS therapies.