Ursolic Acid Triggers Apoptosis in Human Osteosarcoma Cells via Caspase Activation and the ERK1/2 MAPK Pathway

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Ursolic acid (UA) is a natural triterpenoid found in plants with demonstrated anti-cancer properties.
• Apoptosis, or programmed cell death, is a critical mechanism for eliminating tumor cells.

Purpose of the Study:

• To investigate the mechanisms by which ursolic acid induces apoptosis in human osteosarcoma MG-63 cells.
• To explore the role of oxidative stress, mitochondrial pathways, caspases, and MAPK signaling in UA-induced apoptosis.

Main Methods:

• Treatment of MG-63 cells with ursolic acid.
• Analysis of cell viability, cell cycle progression, oxidative stress markers, and mitochondrial membrane potential.
• Western blot analysis for apoptosis-related proteins (caspases, PARP, MAPK pathway proteins, Bax, Bcl-2, XIAP, survivin).
• Inhibition studies using specific caspase and ERK1/2 inhibitors.

Main Results:

• Ursolic acid suppressed MG-63 cell viability and induced cell cycle arrest.
• UA treatment led to increased oxidative stress, mitochondrial dysfunction, and activation of caspases (8, 9, 3) and PARP cleavage.
• UA upregulated activated ERK1/2, JNK, and p38 MAPK.
• Inhibition of caspases and ERK1/2 attenuated UA-induced apoptosis.
• UA treatment increased the Bax/Bcl-2 ratio and decreased XIAP and survivin levels.

Conclusions:

• Ursolic acid effectively induces apoptosis in osteosarcoma MG-63 cells.
• The mechanism involves caspase-dependent and ERK1/2 MAPK-associated pathways.
• UA-induced apoptosis is mediated by oxidative stress, mitochondrial disruption, and modulation of pro- and anti-apoptotic proteins.