Manoalide Induces Intrinsic Apoptosis by Oxidative Stress and Mitochondrial Dysfunction in Human Osteosarcoma Cells

Area of Science:

• Biochemistry
• Oncology
• Marine Natural Products Chemistry

Background:

• Osteosarcoma (OS) is a primary malignant bone tumor with a high mortality rate, especially in metastatic cases.
• Manoalide, a sesterterpenoid from marine sponges, exhibits anti-inflammatory, analgesic, and anti-cancer properties.
• Understanding manoalide's mechanism against OS is crucial for developing new therapeutic strategies.

Purpose of the Study:

• To investigate the cytotoxic effects and underlying mechanisms of manoalide on human osteosarcoma cells (143B and MG63).
• To elucidate manoalide's impact on oxidative stress, mitochondrial function, and apoptosis pathways in OS cells.

Main Methods:

• Treatment of 143B and MG63 cells with varying concentrations of manoalide (10, 20, 40 µM) for 24 and 48 hours.
• Assessment of cell viability, reactive oxygen species (ROS) levels, antioxidant protein expression, and apoptotic markers (caspase-9/-3, PARP).
• Evaluation of mitochondrial function, including oxidative phosphorylation, ATP generation, membrane potential, and mitochondrial dynamics (fusion/fission proteins).

Main Results:

• Manoalide significantly reduced MG63 cell viability in a dose- and time-dependent manner.
• Manoalide induced ROS overproduction, disrupted antioxidant proteins, and activated apoptosis.
• Manoalide impaired mitochondrial function by affecting oxidative phosphorylation, ATP generation, membrane potential, and promoting mitochondrial fragmentation.

Conclusions:

• Manoalide induces osteosarcoma cell death through oxidative stress, mitochondrial dysfunction, and apoptosis.
• N-acetyl-l-cysteine pre-treatment mitigated manoalide-induced toxicity, confirming the role of ROS.
• Manoalide demonstrates potential as an innovative therapeutic agent for human osteosarcoma.